Molecular actions of glucocorticoids in cartilage and bone during health, disease, and steroid therapy

Physiological Reviews

Volumn 96, Issue 2, 2016, Pages 409-447

  Hartmann, Kerstin ^a,b   Koenen, Mascha ^a,b   Schauer, Sebastian ^a,b   Wittig Blaich, Stephanie ^a,b   Ahmad, Mubashir ^a,b   Baschant, Ulrike ^a,b   Tuckermann, Jan P ^a,b  

^a UNIVERSITY OF ULM   (Germany)

^b DRESDEN UNIVERSITY OF TECHNOLOGY   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

GLUCOCORTICOID; GLUCOCORTICOID RECEPTOR; PARATHYROID HORMONE; THYROID HORMONE;

ALTERNATIVE RNA SPLICING; APOPTOSIS; ARTICLE; BONE DENSITY; BONE DISEASE; BONE MASS; BONE REMODELING; CARTILAGE CELL; CATCH UP GROWTH; CELL DIFFERENTIATION; CELL PROLIFERATION; DNA RESPONSIVE ELEMENT; DNA SEQUENCE; FRACTURE; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; GLUCOSE METABOLISM; GROWTH PLATE; HOMEOSTASIS; HUMAN; INSULIN RESISTANCE; NONHUMAN; OSSIFICATION; OSTEOARTHRITIS; OSTEOBLAST; OSTEOCLAST; OSTEOCYTE; OSTEOLYSIS; OSTEOPOROSIS; OSTEOSARCOMA CELL; PRIORITY JOURNAL; PROTEIN PROCESSING; PROTEIN STRUCTURE; RHEUMATOID ARTHRITIS; SIGNAL TRANSDUCTION; STEROID THERAPY; TRANSLATION INITIATION; WNT SIGNALING PATHWAY; ANIMAL; ARTHRITIS, RHEUMATOID; BONE; CARTILAGE; DISEASE MODEL; DRUG EFFECTS; MESENCHYMAL STROMA CELL; METABOLISM;

ANIMALS; ARTHRITIS, RHEUMATOID; BONE AND BONES; BONE REMODELING; CARTILAGE; DISEASE MODELS, ANIMAL; GENE EXPRESSION REGULATION; GLUCOCORTICOIDS; GROWTH PLATE; HUMANS; INSULIN RESISTANCE; MESENCHYMAL STROMAL CELLS; OSTEOARTHRITIS; RECEPTOR CROSS-TALK; RECEPTORS, GLUCOCORTICOID;

EID: 84957065273     PISSN: 00319333     EISSN: 15221210     Source Type: Journal    
DOI: 10.1152/physrev.00011.2015     Document Type: Article

References (435)

1. Abad V, Meyers JL, Weise M, Gafni RI, Barnes KM, Nilsson O, Bacher JD, Baron J. The role of the resting zone in growth plate chondrogenesis. Endocrinology 143: 1851–1857, 2002.
2. Abraham SM, Lawrence T, Kleiman A, Warden P, Medghalchi M, Tuckermann J, Saklatvala J, Clark AR. Anti-inflammatory effects of dexamethasone are partly dependent on induction of dual specificity phosphatase 1. J Exp Med 203: 1883–1889, 2006.
3. Afridi HI, Kazi TG, Talpur FN, Naher S, Brabazon D. Relationship between toxic metals exposure via cigarette smoking and rheumatoid arthritis. Clin Lab 60: 1735–1745, 2014.
4. Albrecht K, Callhoff J, Schneider M, Zink A. High variability in glucocorticoid starting doses in patients with rheumatoid arthritis: observational data from an early arthritis cohort. Rheumatol Int 35: 1377–1384, 2015.
5. Almeida M, Han L, Ambrogini E, Weinstein RS, Manolagas SC. Glucocorticoids and tumor necrosis factor α increase oxidative stress and suppress wnt protein signaling in osteoblasts. J Biol Chem 286: 44326–44335, 2011.
6. Almon RR, DuBois DC, Jin JY, Jusko WJ. Temporal profiling of the transcriptional basis for the development of corticosteroid-induced insulin resistance in rat muscle. J Endocrinol 184: 219–232, 2005.
7. Almon RR, DuBois DC, Yao Z, Hoffman EP, Ghimbovschi S, Jusko WJ. Microarray analysis of the temporal response of skeletal muscle to methylprednisolone: comparative analysis of two dosing regimens. Physiol Genomics 30: 282–299, 2007.
8. Amizuka N, Warshawsky H, Henderson JE, Goltzman D, Karaplis AC. Parathyroid hormone-related peptide-depleted mice show abnormal epiphyseal cartilage development and altered endochondral bone formation. J Cell Biol 126: 1611–1623, 1994.
9. Anbalagan M, Huderson B, Murphy L, Rowan BG. Post-translational modifications of nuclear receptors and human disease. Nuclear Receptor Signal 10: e001, 2012.
10. Annefeld M. Changes in rat epiphyseal cartilage after treatment with dexamethasone and glycosaminoglycan-peptide complex. Pathol Res Pract 188: 649–652, 1992.
11. Arroll B, Goodyear-Smith F. Corticosteroid injections for osteoarthritis of the knee: meta-analysis. BMJ 328: 869, 2004.
12. Arvidson K, Abdallah BM, Applegate LA, Baldini N, Cenni E, Gomez-Barrena E, Granchi D, Kassem M, Konttinen YT, Mustafa K, Pioletti DP, Sillat T, Finne-Wistrand A. Bone regeneration and stem cells. J Cell Mol Med 15: 718–746, 2011.
13. Asada M, Rauch A, Shimizu H, Maruyama H, Miyaki S, Shibamori M, Kawasome H, Ishiyama H, Tuckermann J, Asahara H. DNA binding-dependent glucocorticoid receptor activity promotes adipogenesis via Kruppel-like factor 15 gene expression. Lab Invest 91: 203–215, 2011.
14. Baglio SR, Devescovi V, Granchi D, Baldini N. MicroRNA expression profiling of human bone marrow mesenchymal stem cells during osteogenic differentiation reveals Osterix regulation by miR-31. Gene 527: 321–331, 2013.
15. Bakker MF, Jacobs JW, Welsing PM, Verstappen SM, Tekstra J, Ton E, Geurts MA, van der Werf JH, van Albada-Kuipers GA, Jahangier-de Veen ZN, van der Veen MJ, Verhoef CM, Lafeber FP, Bijlsma JW. Low-dose prednisone inclusion in a methotrexate- based, tight control strategy for early rheumatoid arthritis: a randomized trial. Ann Intern Med 156: 329–339, 2012.
16. Bamberger CM, Bamberger AM, de Castro M, Chrousos GP. Glucocorticoid receptor beta, a potential endogenous inhibitor of glucocorticoid action in humans. J Clin Invest 95: 2435–2441, 1995.
17. Baron R, Kneissel M. WNT signaling in bone homeostasis and disease: from human mutations to treatments. Nature Med 19: 179–192, 2013.
18. Barthel A, Schmoll D, Kruger KD, Bahrenberg G, Walther R, Roth RA, Joost HG. Differential regulation of endogenous glucose-6-phosphatase and phosphoenolpyruvate carboxykinase gene expression by the forkhead transcription factor FKHR in H4IIE-hepatoma cells. Biochem Biophys Res Commun 285: 897–902, 2001.
19. Bartholome B, Spies CM, Gaber T, Schuchmann S, Berki T, Kunkel D, Bienert M, Radbruch A, Burmester GR, Lauster R, Scheffold A, Buttgereit F. Membrane glucocorticoid receptors (mGCR) are expressed in normal human peripheral blood mononuclear cells and up-regulated after in vitro stimulation and in patients with rheumatoid arthritis. FASEB J 18: 70–80, 2004.
20. Baschant U, Frappart L, Rauchhaus U, Bruns L, Reichardt HM, Kamradt T, Bräuer R, Tuckermann JP. Glucocorticoid therapy of antigen-induced arthritis depends on the dimerized glucocorticoid receptor in T cells. Proc Natl Acad Sci USA 108: 19317–19322, 2011.
21. Bazuine M, Carlotti F, Tafrechi RS, Hoeben RC, Maassen JA. Mitogen-activated protein kinase (MAPK) phosphatase-1 and -4 attenuate p38 MAPK during dexamethasone- induced insulin resistance in 3T3–L1 adipocytes. Mol Endocrinol 18: 1697–1707, 2004.
22. Beato M, Arnemann J, Chalepakis G, Slater E, Willmann T. Gene regulation by steroid hormones. J Steroid Biochem 27: 9–14, 1987.
23. Beato M, Herrlich P, Schutz G. Steroid hormone receptors: many actors in search of a plot. Cell 83: 851–857, 1995.
24. Beaulieu E, Ngo D, Santos L, Yang YH, Smith M, Jorgensen C, Escriou V, Scherman D, Courties G, Apparailly F, Morand EF. Glucocorticoid-induced leucine zipper is an endogenous antiinflammatory mediator in arthritis. Arthritis Rheum 62: 2651–2661, 2010.
25. Beavan S, Horner A, Bord S, Ireland D, Compston J. Colocalization of glucocorticoid and mineralocorticoid receptors in human bone. J Bone Miner Res 16: 1496–1504, 2001.
26. Beger C, Gerdes K, Lauten M, Tissing WJ, Fernandez-Munoz I, Schrappe M, Welte K. Expression and structural analysis of glucocorticoid receptor isoform gamma in human leukaemia cells using an isoform-specific real-time polymerase chain reaction approach. Br J Haematol 122: 245–252, 2003.
27. Begovich AB, Carlton VE, Honigberg LA, Schrodi SJ, Chokkalingam AP, Alexander HC, Ardlie KG, Huang Q, Smith AM, Spoerke JM, Conn MT, Chang M, Chang SY, Saiki RK, Catanese JJ, Leong DU, Garcia VE, McAllister LB, Jeffery DA, Lee AT, Batliwalla F, Remmers E, Criswell LA, Seldin MF, Kastner DL, Amos CI, Sninsky JJ, Gregersen PK. A missense single-nucleotide polymorphism in a gene encoding a protein tyrosine phosphatase (PTPN22) is associated with rheumatoid arthritis. Am J Hum Genet 75: 330–337, 2004.
28. Behrens F, Shepard N, Mitchell N. Alterations of rabbit articular cartilage by intraarticular injections of glucocorticoids. J Bone Joint Surg Am 57: 70–76, 1975.
29. Beier F. Cell-cycle control and the cartilage growth plate. J Cell Physiol 202: 1–8, 2005.
30. Bellamy N, Campbell J, Robinson V, Gee T, Bourne R, Wells G. Intra-articular corticosteroid for treatment of osteoarthritis of the knee. Cochrane Database Syst Rev CD005328, 2006.
31. Bellows CG, Aubin JE, Heersche JN. Physiological concentrations of glucocorticoids stimulate formation of bone nodules from isolated rat calvaria cells in vitro. Endocrinology 121: 1985–1992, 1987.
32. Bender IK, Cao Y, Lu NZ. Determinants of the heightened activity of glucocorticoid receptor translational isoforms. Mol Endocrinol 27: 1577–1587, 2013.
33. Biddie SC, John S, Hager GL. Genome-wide mechanisms of nuclear receptor action. Trends Endocrinol Metab 21: 3, 2010.
34. Biddie SC, John S, Sabo PJ, Thurman RE, Johnson TA, Schiltz RL, Miranda TB, Sung MH, Trump S, Lightman SL, Vinson C, Stamatoyannopoulos JA, Hager GL. Transcription factor AP1 potentiates chromatin accessibility and glucocorticoid receptor binding. Mol Cell 43: 145–155, 2011.
35. Binder EB. The role of FKBP5, a co-chaperone of the glucocorticoid receptor in the pathogenesis and therapy of affective and anxiety disorders. Psychoneuroendocrinology 34 Suppl 1: S186–195, 2009.
36. Bjornsdottir S, Saaf M, Bensing S, Kampe O, Michaelsson K, Ludvigsson JF. Risk of hip fracture in Addison’s disease: a population-based cohort study. J Intern Med 270: 187–195, 2011.
37. Bosch P, Musgrave DS, Lee JY, Cummins J, Shuler T, Ghivizzani TC, Evans T, Robbins TD, Huard. Osteoprogenitor cells within skeletal muscle. J Orthop Res 18: 933–944, 2000.
38. Bottini N, Firestein GS. Duality of fibroblast-like synoviocytes in RA: passive responders and imprinted aggressors. Nature Rev Rheumatol 9: 24–33, 2013.
39. Brackertz D, Mitchell GF, Mackay IR. Antigen-induced arthritis in mice. I. Induction of arthritis in various strains of mice. Arthritis Rheum 20: 841–850, 1977.
40. Brennan-Speranza TC, Henneicke H, Gasparini SJ, Blankenstein KI, Heinevetter U, Cogger VC, Svistounov D, Zhang Y, Cooney GJ, Buttgereit F, Dunstan CR, Gundberg C, Zhou H, Seibel MJ. Osteoblasts mediate the adverse effects of glucocorticoids on fuel metabolism. J Clin Invest 122: 4172–4189, 2012.
41. Brunetti G, Faienza MF, Piacente L, Ventura A, Oranger A, Carbone C, Benedetto AD, Colaianni G, Gigante M, Mori G, Gesualdo L, Colucci S, Cavallo L, Grano M. High dickkopf-1 levels in sera and leukocytes from children with 21-hydroxylase deficiency on chronic glucocorticoid treatment. Am J Physiol Endocrinol Metab 304: E546–E554, 2013.
42. Bucci M, Roviezzo F, Cicala C, Sessa WC, Cirino G. Geldanamycin, an inhibitor of heat shock protein 90 (Hsp90) mediated signal transduction has anti-inflammatory effects and interacts with glucocorticoid receptor in vivo. Br J Pharmacol 131: 13–16, 2000.
43. Buckler JM, Willgerodt H, Keller E. Growth in thyrotoxicosis. Arch Dis Child 61: 464–471, 1986.
44. Bujalska IJ, Kumar S, Hewison M, Stewart PM. Differentiation of adipose stromal cells: the roles of glucocorticoids and 11beta-hydroxysteroid dehydrogenase. Endocrinology 140: 3188–3196, 1999.
45. Burd CJ, Archer TK. Chromatin architecture defines the glucocorticoid response. Mol Cell Endocrinol 380: 25–31, 2013.
46. Burdan F, Szumilo J, Korobowicz A, Farooquee R, Patel S, Patel A, Dave A, Szumilo M, Solecki M, Klepacz R, Dudka J. Morphology and physiology of the epiphyseal growth plate. Folia Histochem Cytobiol 47: 5–16, 2009.
47. Buren J, Lai YC, Lundgren M, Eriksson JW, Jensen J. Insulin action and signalling in fat and muscle from dexamethasone-treated rats. Arch Biochem Biophys 474: 91–101, 2008.
48. Butler JS, Queally JM, Devitt BM, Murray DW, Doran PP, O’Byrne JM. Silencing Dkk1 expression rescues dexamethasone-induced suppression of primary human osteoblast differentiation. BMC Musculoskeletal Disorders 11: 210, 2010.
49. + ions into concanavalin A-stimulated thymocytes. Biochem J 326: 329–332, 1997.
50. Buttgereit F, Straub RH, Wehling M, Burmester GR. Glucocorticoids in the treatment of rheumatic diseases: An update on the mechanisms of action. Arthritis Rheum 50: 3408–3417, 2004.
51. Buttgereit F, Zhou H, Kalak R, Gaber T, Spies CM, Huscher D, Straub RH, Modzelewski J, Dunstan CR, Seibel MJ. Transgenic disruption of glucocorticoid signaling in mature osteoblasts and osteocytes attenuates K/BxN mouse serum-induced arthritis in vivo. Arthritis Rheum 60: 1998–2007, 2009.
52. Canalis E, Bilezikian JP, Angeli A, Giustina A. Perspectives on glucocorticoid-induced osteoporosis. Bone 34: 593–598, 2004.
53. Canalis E, Mazziotti G, Giustina A, Bilezikian JP. Glucocorticoid-induced osteoporosis: pathophysiology and therapy. Osteoporosis Int 18: 1319–1328, 2007.
54. Cao Y, Bender IK, Konstantinidis AK, Shin SC, Jewell CM, Cidlowski JA, Schleimer RP, Lu NZ. Glucocorticoid receptor translational isoforms underlie maturational stagespecific glucocorticoid sensitivities of dendritic cells in mice and humans. Blood 121: 1553–1562, 2013.
55. Cárcamo-Orive I, Gaztelumendi A, Delgado J, Tejados N, Dorronsoro A, Fernández- Rueda J, Pennington DJ, Trigueros C. Regulation of human bone marrow stromal cell proliferation and differentiation capacity by glucocorticoid receptor and AP-1 crosstalk. J Bone Miner Res 25: 2115–2125, 2010.
56. Chan CK, Seo EY, Chen JY, Lo D, McArdle A, Sinha R, Tevlin R, Seita J, Vincent- Tompkins J, Wearda T, Lu WJ, Senarath-Yapa K, Chung MT, Marecic O, Tran M, Yan KS, Upton R, Walmsley GG, Lee AS, Sahoo D, Kuo CJ, Weissman IL, Longaker MT. Identification and specification of the mouse skeletal stem cell. Cell 160: 285–298, 2015.
57. Chandra V, Huang P, Hamuro Y, Raghuram S, Wang Y, Burris TP, Rastinejad F. Structure of the intact PPAR-γ-RXR-α nuclear receptor complex on DNA. Nature 456: 350–356, 2008.
58. Chang JK, Li CJ, Liao HJ, Wang CK, Wang GJ, Ho ML. Anti-inflammatory drugs suppress proliferation and induce apoptosis through altering expressions of cell cycle regulators and pro-apoptotic factors in cultured human osteoblasts. Toxicology 258: 148–156, 2009.
59. Chatzopoulou A, Roy U, Meijer AH, Alia A, Spaink HP, Schaaf MJ. Transcriptional and metabolic effects of glucocorticoid receptor alpha and beta signaling in zebrafish. Endocrinology en 20141941, 2015.
60. Chen D, Ma H, Hong H, Koh SS, Huang SM, Schurter BT, Aswad DW, Stallcup MR. Regulation of transcription by a protein methyltransferase. Science 284: 2174–2177, 1999.
61. Cheng X, Chen JL, Ma ZL, Zhang ZL, Lv S, Mai DM, Liu JJ, Chuai M, Lee KKH, Wan C, Yang X. Biphasic influence of dexamethasone exposure on embryonic vertebrate skeleton development. Toxicol Appl Pharmacol 281: 19–29, 2014.
62. Cho YG, Cho ML, Min SY, Kim HY. Type II collagen autoimmunity in a mouse model of human rheumatoid arthritis. Autoimmunity Rev 7: 65–70, 2007.
63. Chover-Gonzalez AJ, Harbuz MS, Lightman SL. Effect of adrenalectomy and stress on interleukin-1 beta-mediated activation of hypothalamic corticotropin-releasing factor mRNA. J Neuroimmunol 42: 155–160, 1993.
64. Chrysis D, Ritzen EM, Savendahl L. Growth retardation induced by dexamethasone is associated with increased apoptosis of the growth plate chondrocytes. J Endocrinol 176: 331–337, 2003.
65. Chrysis D, Zaman F, Chagin AS, Takigawa M, Savendahl L. Dexamethasone induces apoptosis in proliferative chondrocytes through activation of caspases and suppression of the Akt-phosphatidylinositol 3=-kinase signaling pathway. Endocrinology 146: 1391–1397, 2005.
66. Clark AR, Belvisi MG. Maps and legends: the quest for dissociated ligands of the glucocorticoid receptor. Pharmacol Ther 134: 54–67, 2012.
67. Cole TJ, Blendy JA, Monaghan AP, Krieglstein K, Schmid W, Aguzzi A, Fantuzzi G, Hummler E, Unsicker K, Schutz G. Targeted disruption of the glucocorticoid receptor gene blocks adrenergic chromaffin cell development and severely retards lung maturation. Genes Dev 9: 1608–1621, 1995.
68. Conradie MM, Cato AC, Ferris WF, de Wet H, Horsch K, Hough S. MKP-1 knockout does not prevent glucocorticoid-induced bone disease in mice. Calcif Tissue Int 89: 221–227, 2011.
69. Coutinho AE, Gray M, Brownstein DG, Salter DM, Sawatzky DA, Clay S, Gilmour JS, Seckl JR, Savill JS, Chapman KE. 11β-Hydroxysteroid dehydrogenase type 1, but not type 2, deficiency worsens acute inflammation and experimental arthritis in mice. Endocrinology 153: 234–240, 2012.
70. Crockett JC, Rogers MJ, Coxon FP, Hocking LJ, Helfrich MH. Bone remodelling at a glance. J Cell Sci 124: 991–998, 2011.
71. Croxtall JD, Choudhury Q, Flower RJ. Glucocorticoids act within minutes to inhibit recruitment of signalling factors to activated EGF receptors through a receptordependent, transcription-independent mechanism. Br J Pharmacol 130: 289–298, 2000.
72. D’Adamio F, Zollo O, Moraca R, Ayroldi E, Bruscoli S, Bartoli A, Cannarile L, Migliorati G, Riccardi C. A new dexamethasone-induced gene of the leucine zipper family protects T lymphocytes from TCR/CD3-activated cell death. Immunity 7: 803–812, 1997.
73. Dalle Carbonare L, Arlot ME, Chavassieux PM, Roux JP, Portero NR, Meunier PJ. Comparison of trabecular bone microarchitecture and remodeling in glucocorticoidinduced and postmenopausal osteoporosis. J Bone Miner Res 16: 97–103, 2001.
74. Davies TH, Ning YM, Sanchez ER. A new first step in activation of steroid receptors: hormone-induced switching of FKBP51 and FKBP52 immunophilins. J Biol Chem 277: 4597–4600, 2002.
75. De Bosscher K. Selective glucocorticoid receptor modulators. J Steroid Biochem Mol Biol 120: 96–104, 2010.
76. De Bosscher K, Haegeman G. Minireview: latest perspectives on antiinflammatory actions of glucocorticoids. Mol Endocrinol 23: 281–291, 2009.
77. Demonacos C, Tsawdaroglou NC, Djordjevic-Markovic R, Papalopoulou M, Galanopoulos V, Papadogeorgaki S, Sekeris CE. Import of the glucocorticoid receptor into rat liver mitochondria in vivo and in vitro. J Steroid Biochem Mol Biol 46: 401–413, 1993.
78. Dempster DW. Bone histomorphometry in glucocorticoid-induced osteoporosis. J Bone Miner Res 4: 137–141, 1989.
79. Denis M, Gustafsson JA. The Mr approximately 90,000 heat shock protein: an important modulator of ligand and DNA-binding properties of the glucocorticoid receptor. Cancer Res 49: 2275s–2281s, 1989.
80. Dewint P, Gossye V, Bosscher KD, Berghe WV, Beneden KV, Deforce D, Calenbergh SV, Müller-Ladner U, Cruyssen BV, Verbruggen G, Haegeman G, Elewaut D. A plantderived ligand favoring monomeric glucocorticoid receptor conformation with impaired transactivation potential attenuates collagen-induced arthritis. J Immunol 180: 2608–2615, 2008.
81. Diarra D, Stolina M, Polzer K, Zwerina J, Ominsky MS, Dwyer D, Korb A, Smolen J, Hoffmann M, Scheinecker C, van der Heide D, Landewe R, Lacey D, Richards WG, Schett G. Dickkopf-1 is a master regulator of joint remodeling. Nature Med 13: 156–163, 2007.
82. DiBattista JA, Martel-Pelletier J, Wosu LO, Sandor T, Antakly T, Pelletier JP. Glucocorticoid receptor mediated inhibition of interleukin-1 stimulated neutral metalloprotease synthesis in normal human chondrocytes. J Clin Endocrinol Metab 72: 316–326, 1991.
83. Dieppe PA, Lohmander LS. Pathogenesis and management of pain in osteoarthritis. Lancet 365: 965–973, 2005.
84. Doerr P, Pirke KM. Cortisol-induced suppression of plasma testosterone in normal adult males. J Clin Endocrinol Metab 43: 622–629, 1976.
85. Dovio A, Perazzolo L, Osella G, Ventura M, Termine A, Milano E, Bertolotto A, Angeli A. Immediate fall of bone formation and transient increase of bone resorption in the course of high-dose, short-term glucocorticoid therapy in young patients with multiple sclerosis. J Clin Endocrinol Metab 89: 4923–4928, 2004.
86. Drouin J, Sun YL, Chamberland M, Gauthier Y, De Lean A, Nemer M, Schmidt TJ. Novel glucocorticoid receptor complex with DNA element of the hormone-repressed POMC gene. EMBO J 12: 145–156, 1993.
87. Ducy P, Desbois C, Boyce B, Pinero G, Story B, Dunstan C, Smith E, Bonadio J, Goldstein S, Gundberg C, Bradley A, Karsenty G. Increased bone formation in osteocalcin- deficient mice. Nature 382: 448–452, 1996.
88. Durbridge TC, Morris HA, Parsons AM, Parkinson IH, Moore RJ, Porter S, Need AG, Nordin BE, Vernon-Roberts B. Progressive cancellous bone loss in rats after adrenalectomy and oophorectomy. Calcif Tissue Int 47: 383–387, 1990.
89. Eastell R, Reid DM, Compston J, Cooper C, Fogelman I, Francis RM, Hosking DJ, Purdie DW, Ralston SH, Reeve J, Russell RG, Stevenson JC, Torgerson DJ. A UK Consensus Group on management of glucocorticoid-induced osteoporosis: an update. J Intern Med 244: 271–292, 1998.
90. Elbi C, Walker DA, Romero G, Sullivan WP, Toft DO, Hager GL, DeFranco DB. Molecular chaperones function as steroid receptor nuclear mobility factors. Proc Natl Acad Sci USA 101: 2876–2881, 2004.
91. Engelke JA, Hale JE, Suttie JW, Price PA. Vitamin K-dependent carboxylase: utilization of decarboxylated bone Gla protein and matrix Gla protein as substrates. Biochim Biophys Acta 1078: 31–34, 1991.
92. Erson AE, Petty EM. MicroRNAs in development and disease. Clin Genet 74: 296–306, 2008.
93. Espina B, Liang M, Russell RGG, Hulley PA. Regulation of bim in glucocorticoidmediated osteoblast apoptosis. J Cell Physiol 215: 488–496, 2008.
94. Evans RM. The steroid and thyroid hormone receptor superfamily. Science 240: 889–895, 1988.
95. Fang H, Beier F. Mouse models of osteoarthritis: modelling risk factors and assessing outcomes. Nat Rev Rheumatol 10: 413–421, 2014.
96. Farquhar T, Todhunter RJ, Fubini SL, Burton-Wurster N, Lust G. Effect of methylprednisolone and mechanical loading on canine articular cartilage in explant culture. Osteoarthritis Cartilage 4: 55–62, 1996.
97. Ferron M, Hinoi E, Karsenty G, Ducy P. Osteocalcin differentially regulates beta cell and adipocyte gene expression and affects the development of metabolic diseases in wild-type mice. Proc Natl Acad Sci USA 105: 5266–5270, 2008.
98. Ferron M, McKee MD, Levine RL, Ducy P, Karsenty G. Intermittent injections of osteocalcin improve glucose metabolism and prevent type 2 diabetes in mice. Bone 50: 568–575, 2012.
99. Ferron M, Wei J, Yoshizawa T, Fattore AD, DePinho RA, Teti A, Ducy P, Karsenty G. Insulin signaling in osteoblasts integrates bone remodeling and energy metabolism. Cell 142: 296–308, 2010.
100. Friedenstein AJ, Piatetzky S, II, Petrakova KV. Osteogenesis in transplants of bone marrow cells. J Embryol Exp Morphol 16: 381–390, 1966.
101. Frijters R, Fleuren W, Toonen EJM, Tuckermann JP, Reichardt HM, van der Maaden H, van Elsas A, van Lierop MJ, Dokter W, de Vlieg J, Alkema W. Prednisolone-induced differential gene expression in mouse liver carrying wild type or a dimerizationdefective glucocorticoid receptor. BMC Genomics 11: 359, 2010.
102. Fubini SL, Todhunter RJ, Burton-Wurster N, Vernier-Singer M, MacLeod JN. Corticosteroids alter the differentiated phenotype of articular chondrocytes. J Orthop Res 19: 688–695, 2001.
103. Fujita T, Fukuyama R, Enomoto H, Komori T. Dexamethasone inhibits insulin-induced chondrogenesis of ATDC5 cells by preventing PI3K-Akt signaling and DNA binding of Runx2. J Cell Biochem 93: 374–383, 2004.
104. Fulzele K, Clemens TL. Novel functions for insulin in bone. Bone 50: 452–456, 2012.
105. Gabet Y, Noh T, Lee C, Frenkel B. Developmentally regulated inhibition of cell cycle progression by glucocorticoids through repression of cyclin A transcription in primary osteoblast cultures. J Cell Physiol 226: 991–998, 2011.
106. Galigniana MD, Radanyi C, Renoir JM, Housley PR, Pratt WB. Evidence that the peptidylprolyl isomerase domain of the hsp90-binding immunophilin FKBP52 is involved in both dynein interaction and glucocorticoid receptor movement to the nucleus. J Biol Chem 276: 14884–14889, 2001.
107. Galigniana NM, Ballmer LT, Toneatto J, Erlejman AG, Lagadari M, Galigniana MD. Regulation of the glucocorticoid response to stress-related disorders by the Hsp90- binding immunophilin FKBP51. J Neurochem 122: 4–18, 2012.
108. Gametchu B, Watson CS, Wu S. Use of receptor antibodies to demonstrate membrane glucocorticoid receptor in cells from human leukemic patients. FASEB J 7: 1283–1292, 1993.
109. Gardai SJ, Hildeman DA, Frankel SK, Whitlock BB, Frasch SC, Borregaard N, Marrack P, Bratton DL, Henson PM. Phosphorylation of Bax Ser184 by Akt regulates its activity and apoptosis in neutrophils. J Biol Chem 279: 21085–21095, 2004.
110. Gat-Yablonski G, Phillip M. Nutritionally-induced catch-up growth. Nutrients 7: 517–551, 2015.
111. Gaur T, Hussain S, Mudhasani R, Parulkar I, Colby JL, Frederick D, Kream BE, van Wijnen AJ, Stein JL, Stein GS, Jones SN, Lian JB. Dicer inactivation in osteoprogenitor cells compromises fetal survival and bone formation, while excision in differentiated osteoblasts increases bone mass in the adult mouse. Dev Biol 340: 10–21, 2010.
112. Gerber HP, Vu TH, Ryan AM, Kowalski J, Werb Z, Ferrara N. VEGF couples hypertrophic cartilage remodeling, ossification and angiogenesis during endochondral bone formation. Nat Med 5: 623–628, 1999.
113. Gibson GJ, Kohler WJ, Schaffler MB. Chondrocyte apoptosis in endochondral ossification of chick sterna. Dev Dyn 203: 468–476, 1995.
114. Gilbert KA, Rannels SR. Glucocorticoid effects on vitamin K-dependent carboxylase activity and matrix Gla protein expression in rat lung. Am J Physiol Lung Cell Mol Physiol 285: L569–L577, 2003.
115. Giorgino F, Pedrini MT, Matera L, Smith RJ. Specific increase in p85alpha expression in response to dexamethasone is associated with inhibition of insulin-like growth factor-I stimulated phosphatidylinositol 3-kinase activity in cultured muscle cells. J Biol Chem 272: 7455–7463, 1997.
116. Glade MJ, Krook L, Schryver HF, Hintz HF. Morphologic and biochemical changes in cartilage of foals treated with dexamethasone. Cornell Vet 73: 170–192, 1983.
117. Glass CK, Rosenfeld MG. The coregulator exchange in transcriptional functions of nuclear receptors. Genes Dev 14: 121–141, 2000.
118. Goldring MB, Marcu KB. Cartilage homeostasis in health and rheumatic diseases. Arthritis Res Ther 11: 224, 2009.
119. Gossye V, Elewaut D, Bougarne N, Bracke D, Van Calenbergh S, Haegeman G, De Bosscher K. Differential mechanism of NF-B inhibition by two glucocorticoid receptor modulators in rheumatoid arthritis synovial fibroblasts. Arthritis Rheum 60: 3241–3250, 2009.
120. Grad I, Picard D. The glucocorticoid responses are shaped by molecular chaperones. Mol Cell Endocrinol 275: 2–12, 2007.
121. Gregersen PK, Silver J, Winchester RJ. The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis. Arthritis Rheum 30: 1205–1213, 1987.
122. Grøntved L, John S, Baek S, Liu Y, Buckley JR, Vinson C, Aguilera G, Hager GL. C/EBP maintains chromatin accessibility in liver and facilitates glucocorticoid receptor recruitment to steroid response elements. EMBO J 32: 1568–1583, 2013.
123. Guo J, Chung UI, Yang D, Karsenty G, Bringhurst FR, Kronenberg HM. PTH/PTHrP receptor delays chondrocyte hypertrophy via both Runx2-dependent and -independent pathways. Dev Biol 292: 116–128, 2006.
124. Hardy R, Juarez M, Naylor A, Tu J, Rabbitt EH, Filer A, Stewart PM, Buckley CD, Raza K, Cooper MS. Synovial DKK1 expression is regulated by local glucocorticoid metabolism in inflammatory arthritis. Arthritis Res Ther 14: R226, 2012.
125. Hauschka PV, Lian JB, Cole DE, Gundberg CM. Osteocalcin and matrix Gla protein: vitamin K-dependent proteins in bone. Physiol Rev 69: 990–1047, 1989.
126. Hayashi K, Yamaguchi T, Yano S, Kanazawa I, Yamauchi M, Yamamoto M, Sugimoto T. BMP/Wnt antagonists are upregulated by dexamethasone in osteoblasts and reversed by alendronate and PTH: potential therapeutic targets for glucocorticoidinduced osteoporosis. Biochem Biophys Res Commun 379: 261–266, 2009.
127. Heck S, Kullmann M, Gast A, Ponta H, Rahmsdorf HJ, Herrlich P, Cato AC. A distinct modulating domain in glucocorticoid receptor monomers in the repression of activity of the transcription factor AP-1. EMBO J 13: 4087–4095, 1994.
128. Heinrichs AA, Bortell R, Rahman S, Stein JL, Alnemri ES, Litwack G, Lian JB, Stein GS. Identification of multiple glucocorticoid receptor binding sites in the rat osteocalcin gene promoter. Biochemistry 32: 11436–11444, 1993.
129. Heinrichs C, Yanovski JA, Roth AH, Yu YM, Domene HM, Yano K, Cutler GB Jr, Baron J. Dexamethasone increases growth hormone receptor messenger ribonucleic acid levels in liver and growth plate. Endocrinology 135: 1113–1118, 1994.
130. Heinz S, Romanoski CE, Benner C, Glass CK. The selection and function of cell type-specific enhancers. Nature Rev Mol Cell Biol 16: 144–154, 2015.
131. Hnisz D, Abraham BJ, Lee TI, Lau A, Saint-Andre V, Sigova AA, Hoke HA, Young RA. Super-enhancers in the control of cell identity and disease. Cell 155: 934–947, 2013.
132. Hochberg MC. Adult and juvenile rheumatoid arthritis: current epidemiologic concepts. Epidemiol Rev 3: 27–44, 1981.
133. Hofbauer LC, Gori F, Riggs BL, Lacey DL, Dunstan CR, Spelsberg TC, Khosla S. Stimulation of osteoprotegerin ligand and inhibition of osteoprotegerin production by glucocorticoids in human osteoblastic lineage cells: potential paracrine mechanisms of glucocorticoid-induced osteoporosis. Endocrinology 140: 4382–4389, 1999.
134. Hofbauer LC, Lacey DL, Dunstan CR, Spelsberg TC, Riggs BL, Khosla S. Interleukin- 1beta and tumor necrosis factor-alpha, but not interleukin-6, stimulate osteoprotegerin ligand gene expression in human osteoblastic cells. Bone 25: 255–259, 1999.
135. Hofbauer LC, Zeitz U, Schoppet M, Skalicky M, Schuler C, Stolina M, Kostenuik PJ, Erben RG. Prevention of glucocorticoid-induced bone loss in mice by inhibition of RANKL. Arthritis Rheum 60: 1427–1437, 2009.
136. Hofkens W, Grevers LC, Walgreen B, de Vries TJ, Leenen PJ, Everts V, Storm G, van den Berg WB, van Lent PL. Intravenously delivered glucocorticoid liposomes inhibit osteoclast activity and bone erosion in murine antigen-induced arthritis. J Control Release 152: 363–369, 2011.
137. Hollander JL. Intra-articular hydrocortisone in arthritis and allied conditions; a summary of two years’ clinical experience. J Bone Joint Surg Am 35-A: 983–990, 1953.
138. Hong D, Chen HX, Yu HQ, Wang C, Deng HT, Lian QQ, Ge RS. Quantitative proteomic analysis of dexamethasone-induced effects on osteoblast differentiation, proliferation, and apoptosis in MC3T3–E1 cells using SILAC. Osteoporos Int 22: 2175–2186, 2011.
139. Horsch K, de Wet H, Schuurmans MM, Allie-Reid F, Cato ACB, Cunningham J, Burrin JM, Hough FS, Hulley PA. Mitogen-activated protein kinase phosphatase 1/dual specificity phosphatase 1 mediates glucocorticoid inhibition of osteoblast proliferation. Mol Endocrinol 21: 2929–2940, 2007.
140. Hozuki T, Imai T, Tsuda E, Matsumura A, Yamamoto D, Toyoshima T, Suzuki S, Yamauchi R, Hayashi T, Hisahara S, Shimohama S. Response of serum carboxylated and undercarboxylated osteocalcin to risedronate monotherapy and combined therapy with vitamin K(2) in corticosteroid-treated patients: a pilot study. Intern Med 49: 371–376, 2010.
141. Hozumi A, Osaki M, Goto H, Sakamoto K, Inokuchi S, Shindo H. Bone marrow adipocytes support dexamethasone-induced osteoclast differentiation. Biochem Biophys Res Commun 382: 780–784, 2009.
142. Hsueh AJ, Erickson GF. Glucocorticoid inhibition of FSH-induced estrogen production in cultured rat granulosa cells. Steroids 32: 639–648, 1978.
143. Huebner KD, Shrive NG, Frank CB. Dexamethasone inhibits inflammation and cartilage damage in a new model of post-traumatic osteoarthritis. J Orthop Res 32: 566–572, 2014.
144. Iglesias P, Arrieta F, Pinera M, Botella-Carretero JI, Balsa JA, Zamarron I, Menacho M, Diez JJ, Munoz T, Vazquez C. Serum concentrations of osteocalcin, procollagen type 1 N-terminal propeptide and beta-CrossLaps in obese subjects with varying degrees of glucose tolerance. Clin Endocrinol 75: 184–188, 2011.
145. Inoue Y, Nakajima A, Tanaka E, Inoue E, Kobayashi A, Hoshi D, Sugimoto N, Seto Y, Taniguchi A, Momohara S, Yamanaka H. Effect of smoking on remission proportions differs between male and female patients with rheumatoid arthritis: a study based on the IORRA Survey. J Rheumatol. In press.
146. Isaksson OG, Jansson JO, Gause IA. Growth hormone stimulates longitudinal bone growth directly. Science 216: 1237–1239, 1982.
147. Ishida Y, Heersche JN. Glucocorticoid-induced osteoporosis: both in vivo and in vitro concentrations of glucocorticoids higher than physiological levels attenuate osteoblast differentiation. J Bone Miner Res 13: 1822–1826, 1998.
148. Islander U, Jochems C, Stubelius A, Andersson A, Lagerquist MK, Ohlsson C, Carlsten H. Combined treatment with dexamethasone and raloxifene totally abrogates osteoporosis and joint destruction in experimental postmenopausal arthritis. Arthritis Res Ther 13: R96, 2011.
149. Jaaskelainen T, Makkonen H, Palvimo JJ. Steroid up-regulation of FKBP51 and its role in hormone signaling. Curr Opin Pharmacol 11: 326–331, 2011.
150. James CB, Uhl TL. A review of articular cartilage pathology and the use of glucosamine sulfate. J Athletic Training 36: 413–419, 2001.
151. James CG, Ulici V, Tuckermann J, Underhill TM, Beier F. Expression profiling of Dexamethasone-treated primary chondrocytes identifies targets of glucocorticoid signalling in endochondral bone development. BMC Genomics 8: 205, 2007.
152. Jensen TW, Hansen MS, Horslev-Petersen K, Hyldstrup L, Abrahamsen B, Langdahl B, Zerahn B, Podenphant J, Stengaard-Petersen K, Junker P, Ostergaard M, Lottenburger T, Ellingsen T, Andersen LS, Hansen I, Skjodt H, Pedersen JK, Lauridsen UB, Svendsen AJ, Tarp U, Lindegaard H, Jurik AG, Vestergaard A, Hetland ML. Periarticular and generalised bone loss in patients with early rheumatoid arthritis: influence of alendronate and intra-articular glucocorticoid treatment. Post hoc analyses from the CIMESTRA trial. Ann Rheum Dis 73: 1123–1129, 2014.
153. Jewell CM, Scoltock AB, Hamel BL, Yudt MR, Cidlowski JA. Complex human glucocorticoid receptor dim mutations define glucocorticoid induced apoptotic resistance in bone cells. Mol Endocrinol 26: 244–256, 2012.
154. Jia D, O’Brien CA, Stewart SA, Manolagas SC, Weinstein RS. Glucocorticoids act directly on osteoclasts to increase their life span and reduce bone density. Endocrinology 147: 5592–5599, 2006.
155. Jia J, Yao W, Guan M, Dai W, Shahnazari M, Kar R, Bonewald L, Jiang JX, Lane NE. Glucocorticoid dose determines osteocyte cell fate. FASEB J 25: 3366–3376, 2011.
156. Jilka RL, Noble B, Weinstein RS. Osteocyte apoptosis. Bone 54: 264–271, 2013.
157. Joanny E, Ding Q, Gong L, Kong P, Saklatvala J, Clark AR. Anti-inflammatory effects of selective glucocorticoid receptor modulators are partially dependent on up-regulation of dual specificity phosphatase 1. Br J Pharmacol 165: 1124–1136, 2012.
158. John S, Sabo PJ, Thurman RE, Sung MH, Biddie SC, Johnson TA, Hager GL, Stamatoyannopoulos JA. Chromatin accessibility pre-determines glucocorticoid receptor binding patterns. Nat Genet 43: 264–268, 2011.
159. Jones E, Churchman SM, English A, Buch MH, Horner EA, Burgoyne CH, Reece R, Kinsey S, Emery P, McGonagle D, Ponchel F. Mesenchymal stem cells in rheumatoid synovium: enumeration and functional assessment in relation to synovial inflammation level. Ann Rheum Dis 69: 450–457, 2010.
160. Jux C, Leiber K, Hugel U, Blum W, Ohlsson C, Klaus G, Mehls O. Dexamethasone impairs growth hormone (GH)-stimulated growth by suppression of local insulin-like growth factor (IGF)-I production and expression of GH- and IGF-I-receptor in cultured rat chondrocytes. Endocrinology 139: 3296–3305, 1998.
161. Kadmiel M, Cidlowski JA. Glucocorticoid receptor signaling in health and disease. Trends Pharmacol Sci 34: 518–530, 2013.
162. Kalak R, Zhou H, Street J, Day RE, Modzelewski JR, Spies CM, Liu PY, Li G, Dunstan CR, Seibel MJ. Endogenous glucocorticoid signalling in osteoblasts is necessary to maintain normal bone structure in mice. Bone 45: 61–67, 2009.
163. Kapinas K, Kessler C, Ricks T, Gronowicz G, Delany AM. miR-29 modulates Wnt signaling in human osteoblasts through a positive feedback loop. J Biol Chem 285: 25221–25231, 2010.
164. Kapinas K, Kessler CB, Delany AM. miR-29 suppression of osteonectin in osteoblasts: regulation during differentiation and by canonical Wnt signaling. J Cell Biochem 108: 216–224, 2009.
165. Karsenty G, Ferron M. The contribution of bone to whole-organism physiology. Nature 481: 314–320, 2012.
166. Kassel O, Sancono A, Krätzschmar J, Kreft B, Stassen M, Cato ACB. Glucocorticoids inhibit MAP kinase via increased expression and decreased degradation of MKP-1. EMBO J 20: 7108–7116, 2001.
167. Kassel O, Schneider S, Heilbock C, Litfin M, Göttlicher M, Herrlich P. A nuclear isoform of the focal adhesion LIM-domain protein Trip6 integrates activating and repressing signals at AP-1- and NF-kappaB-regulated promoters. Genes Dev 18: 2518–2528, 2004.
168. Kato Y, Gospodarowicz D. Stimulation by glucocorticoid of the synthesis of cartilagematrix proteoglycans produced by rabbit costal chondrocytes in vitro. J Biol Chem 260: 2364–2373, 1985.
169. Keating KM, Roess DA, Peacock JS, Barisas BG. Glucocorticoid effects on membrane lipid mobility during differentiation of murine B lymphocytes. Biochim Biophys Acta 846: 305–312, 1985.
170. Kelly A, Bowen H, Jee YK, Mahfiche N, Soh C, Lee T, Hawrylowicz C, Lavender P. The glucocorticoid receptor beta isoform can mediate transcriptional repression by recruiting histone deacetylases. J Allergy Clin Immunol 121: 203–208. e201, 2008.
171. Kim HJ, Zhao H, Kitaura H, Bhattacharyya S, Brewer JA, Muglia LJ, Ross FP, Teitelbaum SL. Glucocorticoids suppress bone formation via the osteoclast. J Clin Invest 116: 2152–2160, 2006.
172. Kim SH, Kim DH, Lavender P, Seo JH, Kim YS, Park JS, Kwak SJ, Jee YK. Repression of TNF-α-induced IL-8 expression by the glucocorticoid receptor-β involves inhibition of histone H4 acetylation. Exp Mol Med 41: 297–306, 2009.
173. Kindblom JM, Ohlsson C, Ljunggren O, Karlsson MK, Tivesten A, Smith U, Mellstrom D. Plasma osteocalcin is inversely related to fat mass and plasma glucose in elderly Swedish men. J Bone Miner Res 24: 785–791, 2009.
174. Kino T, Su YA, Chrousos GP. Human glucocorticoid receptor (GR) isoform β: recent understanding of its potential implications in physiology and pathophysiology. Cell Mol Life Sci 66: 3435–3448, 2009.
175. Kirwan J, Power L. Glucocorticoids: action and new therapeutic insights in rheumatoid arthritis. Curr Opin Rheumatol 19: 233–237, 2007.
176. Kleiman A, Hubner S, Rodriguez Parkitna JM, Neumann A, Hofer S, Weigand MA, Bauer M, Schmid W, Schutz G, Libert C, Reichardt HM, Tuckermann JP. Glucocorticoid receptor dimerization is required for survival in septic shock via suppression of interleukin-1 in macrophages. FASEB J 26: 722–729, 2012.
177. Klengel T, Mehta D, Anacker C, Rex-Haffner M, Pruessner JC, Pariante CM, Pace TWW, Mercer KB, Mayberg HS, Bradley B, Nemeroff CB, Holsboer F, Heim CM, Ressler KJ, Rein T, Binder EB. Allele-specific FKBP5 DNA demethylation mediates gene-childhood trauma interactions. Nature Neurosci 16: 33–41, 2013.
178. Ko JY, Chuang PC, Chen MW, Ke HC, Wu SL, Chang YH, Chen YS, Wang FS. MicroRNA-29a ameliorates glucocorticoid-induced suppression of osteoblast differentiation by regulating beta-catenin acetylation. Bone 57: 468–475, 2013.
179. Kobayashi T, Lu J, Cobb BS, Rodda SJ, McMahon AP, Schipani E, Merkenschlager M, Kronenberg HM. Dicer-dependent pathways regulate chondrocyte proliferation and differentiation. Proc Natl Acad Sci USA 105: 1949–1954, 2008.
180. Koedam JA, Smink JJ, van Buul-Offers SC. Glucocorticoids inhibit vascular endothelial growth factor expression in growth plate chondrocytes. Mol Cell Endocrinol 197: 35–44, 2002.
181. Koromila T, Baniwal SK, Song YS, Martin A, Xiong J, Frenkel B. Glucocorticoids antagonize RUNX2 during osteoblast differentiation in cultures of ST2 pluripotent mesenchymal cells. J Cell Biochem 115: 27–33, 2014.
182. Kovacs JJ, Murphy PJ, Gaillard S, Zhao X, Wu JT, Nicchitta CV, Yoshida M, Toft DO, Pratt WB, Yao TP. HDAC6 regulates Hsp90 acetylation and chaperone-dependent activation of glucocorticoid receptor. Mol Cell 18: 601–607, 2005.
183. Kronenberg HM. Developmental regulation of the growth plate. Nature 423: 332–336, 2003.
184. Kumar R, Thompson EB. Gene regulation by the glucocorticoid receptor: structure: function relationship. J Steroid Biochem Mol Biol 94: 383–394, 2005.
185. Kuo T, Lew MJ, Mayba O, Harris CA, Speed TP, Wang JC. Genome-wide analysis of glucocorticoid receptor-binding sites in myotubes identifies gene networks modulating insulin signaling. Proc Natl Acad Sci USA 109: 11160–11165, 2012.
186. Lam J, Takeshita S, Barker JE, Kanagawa O, Ross FP, Teitelbaum SL. TNF-alpha induces osteoclastogenesis by direct stimulation of macrophages exposed to permissive levels of RANK ligand. J Clin Invest 106: 1481–1488, 2000.
187. Lane NE, Yao W, Balooch M, Nalla RK, Balooch G, Habelitz S, Kinney JH, Bonewald LF. Glucocorticoid-treated mice have localized changes in trabecular bone material properties and osteocyte lacunar size that are not observed in placebo-treated or estrogen-deficient mice. J Bone Miner Res 21: 466–476, 2006.
188. Langlais D, Couture C, Balsalobre A, Drouin J. The Stat3/GR interaction code: predictive value of direct/indirect DNA recruitment for transcription outcome. Mol Cell 1–31, 2012.
189. Lawrence RC, Felson DT, Helmick CG, Arnold LM, Choi H, Deyo RA, Gabriel S, Hirsch R, Hochberg MC, Hunder GG, Jordan JM, Katz JN, Kremers HM, Wolfe F, National Arthritis Data. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States Part II. Arthritis Rheum 58: 26–35, 2008.
190. Lee NK, Sowa H, Hinoi E, Ferron M, Ahn JD, Confavreux C, Dacquin R, Mee PJ, McKee MD, Jung DY, Zhang Z, Kim JK, Mauvais-Jarvis F, Ducy P, Karsenty G. Endocrine regulation of energy metabolism by the skeleton. Cell 130: 456–469, 2007.
191. Leech M, Metz C, Hall P, Hutchinson P, Gianis K, Smith M, Weedon H, Holdsworth SR, Bucala R, Morand EF. Macrophage migration inhibitory factor in rheumatoid arthritis: evidence of proinflammatory function and regulation by glucocorticoids. Arthritis Rheum 42: 1601–1608, 1999.
192. Lekva T, Bollerslev J, Kristo C, Olstad OK, Ueland T, Jemtland R. The glucocorticoidinduced leucine zipper gene (GILZ) expression decreases after successful treatment of patients with endogenous Cushing’s syndrome and may play a role in glucocorticoid- induced osteoporosis. J Clin Endocrinol Metab 95: 246–255, 2010.
193. Lewis-Tuffin LJ, Cidlowski JA. The physiology of human glucocorticoid receptor beta (hGRbeta) and glucocorticoid resistance. Ann NY Acad Sci 1069: 1–9, 2006.
194. Li A, Hardy R, Stoner S, Tuckermann J, Seibel M, Zhou H. Deletion of mesenchymal glucocorticoid receptor attenuates embryonic lung development and abdominal wall closure. PLoS One 8: e63578, 2013.
195. Li H, Qian W, Weng X, Wu Z, Li H, Zhuang Q, Feng B, Bian Y. Glucocorticoid receptor and sequential P53 activation by dexamethasone mediates apoptosis and cell cycle arrest of osteoblastic MC3T3–E1 cells. PLoS One 7: e37030, 2012.
196. Li J, Zhang N, Huang X, Xu J, Fernandes JC, Dai K, Zhang X. Dexamethasone shifts bone marrow stromal cells from osteoblasts to adipocytes by C/EBPalpha promoter methylation. Cell Death Dis 4: e832, 2013.
197. Li LB, Leung DYM, Martin RJ, Goleva E. Inhibition of histone deacetylase 2 expression by elevated glucocorticoid receptor β in steroid-resistant asthma. Am J Respir Crit Care Med 182: 877–883, 2010.
198. Li P, Schwarz EM. The TNF-alpha transgenic mouse model of inflammatory arthritis. Springer Semin Immunopathol 25: 19–33, 2003.
199. Li P, Schwarz EM, O’keefe RJ, Ma L, Boyce BF, Xing L. RANK signaling is not required for TNFalpha-mediated increase in CD11(hi) osteoclast precursors but is essential for mature osteoclast formation in TNFalpha-mediated inflammatory arthritis. J Bone Miner Res 19: 207–213, 2004.
200. Li T, Li H, Li T, Fan J, Zhao RC, Weng X. MicroRNA expression profile of dexamethasone- induced human bone marrow-derived mesenchymal stem cells during osteogenic differentiation. J Cell Biochem 115: 1683–1691, 2014.
201. Li X, Jin L, Cui Q, Wang GJ, Balian G. Steroid effects on osteogenesis through mesenchymal cell gene expression. Osteoporos Int 16: 101–108, 2005.
202. Li Z, Hassan MQ, Jafferji M, Aqeilan RI, Garzon R, Croce CM, van Wijnen AJ, Stein JL, Stein GS, Lian JB. Biological functions of miR-29b contribute to positive regulation of osteoblast differentiation. J Biol Chem 284: 15676–15684, 2009.
203. Lim HW, Uhlenhaut NH, Rauch A, Weiner J, Hübner S, Hübner N, Won KJ, Lazar MA, Tuckermann J, Steger DJ. Genomic redistribution of GR monomers and dimers mediates transcription response to exogenous glucocorticoid In vivo. Genome Res 25: 836–844, 2015.
204. Limbourg FP, Huang Z, Plumier JC, Simoncini T, Fujioka M, Tuckermann J, Schütz G, Moskowitz MA, Liao JK. Rapid nontranscriptional activation of endothelial nitric oxide synthase mediates increased cerebral blood flow and stroke protection by corticosteroids. J Clin Invest 110: 1729–1738, 2002.
205. Lin CS, Xin ZC, Deng CH, Ning H, Lin G, Lue TF. Defining adipose tissue-derived stem cells in tissue and in culture. Histol Histopathol 25: 807–815, 2010.
206. Lin JP, Cash JM, Doyle SZ, Peden S, Kanik K, Amos CI, Bale SJ, Wilder RL. Familial clustering of rheumatoid arthritis with other autoimmune diseases. Hum Genet 103: 475–482, 1998.
207. Liu-Bryan R, Terkeltaub R. Emerging regulators of the inflammatory process in osteoarthritis. Nat Rev Rheumatol 11: 35–44, 2015.
208. Lovén J, Hoke HA, Lin CY, Lau A, Orlando DA, Vakoc CR, Bradner JE, Lee TI, Young RA. Selective inhibition of tumor oncogenes by disruption of super-enhancers. Cell 153: 320–334, 2013.
209. Löwenberg M, Stahn C, Hommes DW, Buttgereit F. Novel insights into mechanisms of glucocorticoid action and the development of new glucocorticoid receptor ligands. Steroids 73: 1025–1029, 2008.
210. Löwenberg M, Tuynman J, Bilderbeek J, Gaber T, Buttgereit F, van Deventer S, Peppelenbosch M, Hommes D. Rapid immunosuppressive effects of glucocorticoids mediated through Lck and Fyn. Blood 106: 1703–1710, 2005.
211. Löwenberg M, Verhaar AP, Bilderbeek J, Marle JV, Buttgereit F, Peppelenbosch MP, Van Deventer SJ, Hommes DW. Glucocorticoids cause rapid dissociation of a T-cellreceptor- associated protein complex containing LCK and FYN. EMBO Reports 7: 1023–1029, 2006.
212. Lu NZ, Cidlowski JA. Translational regulatory mechanisms generate N-terminal glucocorticoid receptor isoforms with unique transcriptional target genes. Mol Cell 18: 331–342, 2005.
213. Lu NZ, Collins JB, Grissom SF, Cidlowski JA. Selective Regulation of Bone Cell Apoptosis by Translational Isoforms of the Glucocorticoid Receptor. Mol Cell Biol 27: 7143–7160, 2007.
214. Lu YC, Evans CH, Grodzinsky AJ. Effects of short-term glucocorticoid treatment on changes in cartilage matrix degradation and chondrocyte gene expression induced by mechanical injury and inflammatory cytokines. Arthritis Res Ther 13: R142, 2011.
215. Lui JC, Nilsson O, Baron J. Growth plate senescence and catch-up growth. Endocr Dev 21: 23–29, 2011.
216. Luppen CA, Smith E, Spevak L, Boskey AL, Frenkel B. Bone morphogenetic protein-2 restores mineralization in glucocorticoid-inhibited MC3T3–E1 osteoblast cultures. J Bone Miner Res 18: 1186–1197, 2003.
217. Ma H, Baumann CT, Li H, Strahl BD, Rice R, Jelinek MA, Aswad DW, Allis CD, Hager GL, Stallcup MR. Hormone-dependent, CARM1-directed, arginine-specific methylation of histone H3 on a steroid-regulated promoter. Curr Biol 11: 1981–1985, 2001.
218. Macrae VE, Ahmed SF, Mushtaq T, Farquharson C. IGF-I signalling in bone growth: inhibitory actions of dexamethasone and IL-1beta. Growth Horm IGF Res 17: 435–439, 2007.
219. Mak W, Shao X, Dunstan CR, Seibel MJ, Zhou H. Biphasic glucocorticoid-dependent regulation of Wnt expression and its inhibitors in mature osteoblastic cells. Calcif Tissue Int 85: 538–545, 2009.
220. Mancini T, Doga M, Mazziotti G, Giustina A. Cushing’s syndrome and bone. Pituitary 7: 249–252, 2004.
221. Mangelsdorf DJ, Thummel C, Beato M, Herrlich P, Schutz G, Umesono K, Blumberg B, Kastner P, Mark M, Chambon P, Evans RM. The nuclear receptor superfamily: the second decade. Cell 83: 835–839, 1995.
222. Marenzana M, Greenslade K, Eddleston A, Okoye R, Marshall D, Moore A, Robinson MK. Sclerostin antibody treatment enhances bone strength but does not prevent growth retardation in young mice treated with dexamethasone. Arthritis Rheum 63: 2385–2395, 2011.
223. Maricar N, Callaghan MJ, Felson DT, O’Neill TW. Predictors of response to intraarticular steroid injections in knee osteoarthritis–a systematic review. Rheumatology 52: 1022–1032, 2013.
224. Martin A, Liu S, David V, Li H, Karydis A, Feng JQ, Quarles LD. Bone proteins PHEX and DMP1 regulate fibroblastic growth factor Fgf23 expression in osteocytes through a common pathway involving FGF receptor (FGFR) signaling. FASEB J 25: 2551–2562, 2011.
225. Mazziotti G, Angeli A, Bilezikian JP, Canalis E, Giustina A. Glucocorticoid-induced osteoporosis: an update. Trends Endocrinol Metab 17: 144–149, 2006.
226. McDonough AK, Curtis JR, Saag KG. The epidemiology of glucocorticoid-associated adverse events. Curr Opin Rheumatol 20: 131–137, 2008.
227. McGarry JG, Daruwalla ZJ. The efficacy, accuracy and complications of corticosteroid injections of the knee joint. Knee Surg Sports Traumatol Arthrosc 19: 1649–1654, 2011.
228. Meijsing SH, Pufall MA, So AY, Bates DL, Chen L, Yamamoto KR. DNA Binding Site Sequence Directs Glucocorticoid Receptor Structure and Activity. Science 324: 407–410, 2009.
229. Mendel DB, Bodwell JE, Gametchu B, Harrison RW, Munck A. Molybdate-stabilized nonactivated glucocorticoid-receptor complexes contain a 90-kDa non-steroid-binding phosphoprotein that is lost on activation. J Biol Chem 261: 3758–3763, 1986.
230. Mikami Y, Asano M, Honda MJ, Takagi M. Bone morphogenetic protein 2 and dexamethasone synergistically increase alkaline phosphatase levels through JAK/STAT signaling in C3H10T1/2 cells. J Cell Physiol 223: 123–133, 2010.
231. Mikami Y, Lee M, Irie S, Honda MJ. Dexamethasone modulates osteogenesis and adipogenesis with regulation of osterix expression in rat calvaria-derived cells. J Cell Physiol 226: 739–748, 2011.
232. Misharin AV, Cuda CM, Saber R, Turner JD, Gierut AK, Haines GK 3rd, Berdnikovs S, Filer A, Clark AR, Buckley CD, Mutlu GM, Budinger GR, and Perlman H. Nonclassical Ly6C(-) monocytes drive the development of inflammatory arthritis in mice. Cell Rep 9: 591–604, 2014.
233. Mittelstadt PR, Monteiro JP, Ashwell JD. Thymocyte responsiveness to endogenous glucocorticoids is required for immunological fitness. J Clin Invest 122: 2384–2394, 2012.
234. Miyazaki Y, Tsukazaki T, Hirota Y, Yonekura A, Osaki M, Shindo H, Yamashita S. Dexamethasone inhibition of TGF beta-induced cell growth and type II collagen mRNAexpression through ERK-integrated AP-1 activity in cultured rat articular chondrocytes. Osteoarthritis Cartilage 8: 378–385, 2000.
235. Mizoguchi F, Izu Y, Hayata T, Hemmi H, Nakashima K, Nakamura T, Kato S, Miyasaka N, Ezura Y, Noda M. Osteoclast-specific Dicer gene deficiency suppresses osteoclastic bone resorption. J Cell Biochem 109: 866–875, 2010.
236. Monach PA, Mathis D, Benoist C. The K/BxN arthritis model. In: Current Protocols in Immunology, edited by Coligan JE. Hoboken, NJ: Wiley Interscience, 2008, chapt. 15, unit 15.22.
237. Monroe DG, McGee-Lawrence ME, Oursler MJ, Westendorf JJ. Update on Wnt signaling in bone cell biology and bone disease. Gene 492: 1–18, 2012.
238. Mourelatos Z. Small RNAs: the seeds of silence. Nature 455: 44–45, 2008.
239. Moutsatsou P, Kassi E, Papavassiliou AG. Glucocorticoid receptor signaling in bone cells. Trends Mol Med 18: 348–359, 2012.
240. Murphy L, Helmick CG. The impact of osteoarthritis in the United States: a population- health perspective. Am J Nurs 112: S13–19, 2012.
241. Mushtaq T, Farquharson C, Seawright E, Ahmed SF. Glucocorticoid effects on chondrogenesis, differentiation and apoptosis in the murine ATDC5 chondrocyte cell line. J Endocrinol 175: 705–713, 2002.
242. Nakae J, Kitamura T, Silver DL, Accili D. The forkhead transcription factor Foxo1 (Fkhr) confers insulin sensitivity onto glucose-6-phosphatase expression. J Clin Invest 108: 1359–1367, 2001.
243. Nakamura M, Watanabe J, Ogawa R, Kanamura S. Immunohistochemical localization of type II and type I collagens in articular cartilage of the femoral head of dexamethasone- treated rats. Histochem J 29: 645–654, 1997.
244. Nakashima T, Hayashi M, Fukunaga T, Kurata K, Oh-Hora M, Feng JQ, Bonewald LF, Kodama T, Wutz A, Wagner EF, Penninger JM, Takayanagi H. Evidencefor osteocyte regulation ofbone homeostasis through RANKL expression. Nat Med 17: 1231–1234, 2011.
245. Nanus DE, Filer AD, Hughes B, Fisher BA, Taylor PC, Stewart PM, Buckley CD, McInnes I, Cooper MS, Raza K. TNFalpha regulates cortisol metabolism in vivo in patients with inflammatory arthritis. Ann Rheum Dis 74: 464–469, 2015.
246. Nasiri M, Nikolaou N, Parajes S, Krone NP, Valsamakis G, Mastorakos G, Hughes B, Taylor A, Bujalska IJ, Gathercole LL, Tomlinson JW. 5α-Reductase type 2 regulates glucocorticoid action and metabolic phenotype in human hepatocytes. Endocrinology 156: 2863–2871, 2015.
247. Naves MA, Pereira RM, Comodo AN, de Alvarenga EL, Caparbo VF, Teixeira VP. Effect of dexamethasone on human osteoblasts in culture: involvement of beta1 integrin and integrin-linked kinase. Cell Biol Int 35: 1147–1151, 2011.
248. Ngo D, Beaulieu E, Gu R, Leaney A, Santos L, Fan H, Yang Y, Kao W, Xu J, Escriou V, Loiler S, Vervoordeldonk MJ, Morand EF. Divergent effects of endogenous and exogenous glucocorticoid-induced leucine zipper in animal models of inflammation and arthritis. Arthritis Rheum 65: 1203–1212, 2013.
249. Nicolaides NC, Galata Z, Kino T, Chrousos GP, Charmandari E. The human glucocorticoid receptor: molecular basis of biologic function. Steroids 75: 1, 2010.
250. Nixon M, Andrew R, Chapman KE. It takes two to tango: dimerisation of glucocorticoid receptor and its anti-inflammatory functions. Steroids 78: 59–68, 2013.
251. Noack C, Hempel U, Preissler C, Dieter P. Prostaglandin E2 impairs osteogenic and facilitates adipogenic differentiation of human bone marrow stromal cells. Prostaglandins Leukot Essent Fatty Acids 94: 91–98, 2015.
252. Nuttall ME, Gimble JM. Is there a therapeutic opportunity to either prevent or treat osteopenic disorders by inhibiting marrow adipogenesis? Bone 27: 177–184, 2000.
253. Nuttall ME, Patton AJ, Olivera DL, Nadeau DP, Gowen M. Human trabecular bone cells are able to express both osteoblastic and adipocytic phenotype: implications for osteopenic disorders. J Bone Miner Res 13: 371–382, 1998.
254. O’Brien CA, Jia D, Plotkin LI, Bellido T, Powers CC, Stewart SA, Manolagas SC, Weinstein RS. Glucocorticoids act directly on osteoblasts and osteocytes to induce their apoptosis and reduce bone formation and strength. Endocrinology 145: 1835–1841, 2004.
255. Oakley RH, Cidlowski JA. The biology of the glucocorticoid receptor: new signaling mechanisms in health and disease. J Allergy Clin Immunol 132: 1033–1044, 2013.
256. Oakley RH, Cidlowski JA. Cellular processing of the glucocorticoid receptor gene and protein: new mechanisms for generating tissue-specific actions of glucocorticoids. J Biol Chem 286: 3177–3184, 2011.
257. Oakley RH, Sar M, Cidlowski JA. The human glucocorticoid receptor beta isoform. Expression, biochemical properties, and putative function. J Biol Chem 271: 9550–9559, 1996.
258. Ohlsson C, Nilsson A, Isaksson O, Lindahl A. Growth hormone induces multiplication of the slowly cycling germinal cells of the rat tibial growth plate. Proc Natl Acad Sci USA 89: 9826–9830, 1992.
259. Ohnaka K, Tanabe M, Kawate H, Nawata H, Takayanagi R. Glucocorticoid suppresses the canonical Wnt signal in cultured human osteoblasts. Biochem Biophys Res Commun 329: 177–181, 2005.
260. Okano T, Koike T, Tada M, Sugioka Y, Mamoto K, Wakitani S, Nakamura H. The limited effects of anti-tumor necrosis factor blockade on bone health in patients with rheumatoid arthritis under the use of glucocorticoid. J Bone Miner Metab 32: 593–600, 2014.
261. Orlov I, Rochel N, Moras D, Klaholz BP. Structure of the full human RXR/VDR nuclear receptor heterodimer complex with its DR3 target DNA. EMBO J 31: 291–300, 2012.
262. Oskowitz AZ, Lu J, Penfornis P, Ylostalo J, McBride J, Flemington EK, Prockop DJ, Pochampally R. Human multipotent stromal cells from bone marrow and microRNA: regulation of differentiation and leukemia inhibitory factor expression. Proc Natl Acad Sci USA 105: 18372–18377, 2008.
263. Owen HC, Roberts SJ, Ahmed SF, Farquharson C. Dexamethasone-induced expression of the glucocorticoid response gene lipocalin 2 in chondrocytes. Am J Physiol Endocrinol Metab 294: E1023–E1034, 2008.
264. Pan G, Cao J, Yang N, Ding K, Fan C, Xiong WC, Hamrick M, Isales CM, Shi XM. Role of glucocorticoid-induced leucine zipper (GILZ) in bone acquisition. J Biol Chem 289: 19373–19382, 2014.
265. Paska W, McDonald KJ, Croft M. Studies on type II collagen induced arthritis in mice. Agents Actions 18: 413–420, 1986.
266. Patel HB, Kornerup KN, Sampaio ALF, D’Acquisto F, Seed MP, Girol AP, Gray M, Pitzalis C, Oliani SM, Perretti M. The impact of endogenous annexin A1 on glucocorticoid control of inflammatory arthritis. Ann Rheumatic Dis 71: 1872–1880, 2012.
267. Patel R, Williams-Dautovich J, Cummins CL. Minireview: new molecular mediators of glucocorticoid receptor activity in metabolic tissues. Mol Endocrinol 28: 999–1011, 2014.
268. Pelletier JP, DiBattista JA, Raynauld JP, Wilhelm S, Martel-Pelletier J. The in vivo effects of intraarticular corticosteroid injections on cartilage lesions, stromelysin, interleukin- 1, and oncogene protein synthesis in experimental osteoarthritis. Lab Invest 72: 578–586, 1995.
269. Pelletier JP, Martel-Pelletier J. Protective effects of corticosteroids on cartilage lesions and osteophyte formation in the Pond-Nuki dog model of osteoarthritis. Arthritis Rheum 32: 181–193, 1989.
270. Pelletier JP, Martel-Pelletier J, Cloutier JM, Woessner JF Jr. Proteoglycan-degrading acid metalloprotease activity in human osteoarthritic cartilage, and the effect of intraarticular steroid injections. Arthritis Rheum 30: 541–548, 1987.
271. Pelletier JP, Mineau F, Raynauld JP, Woessner JF Jr, Gunja-Smith Z, Martel-Pelletier J. Intra-articular injections with methylprednisolone acetate reduce osteoarthritic lesions in parallel with chondrocyte stromelysin synthesis in experimental osteoarthritis. Arthritis Rheum 37: 414–423, 1994.
272. Pereira RC, Delany AM, Canalis E. Effects of cortisol and bone morphogenetic protein- 2 on stromal cell differentiation: correlation with CCAAT-enhancer binding protein expression. Bone 30: 685–691, 2002.
273. Pereira RMR, Delany AM, Durant D, Canalis E. Cortisol regulates the expression of Notch in osteoblasts. J Cell Biochem 85: 252–258, 2002.
274. Perretti M, Mugridge KG, Becherucci C, Parente L. Evidence that interleukin-1 and lipoxygenase metabolites mediate the lethal effect of complete Freund’s adjuvant in adrenalectomized rats. Lymphokine Cytokine Res 10: 239–243, 1991.
275. Pfeiffer BM, Krenzer S, Dockhorn R, Schwenke R, Schwenke H, Waehrisch J, Kraus E. Impact of modified-release prednisone on functional ability in patients with rheumatoid arthritis. Rheumatol Int 33: 1447–1454, 2013.
276. Piemontese M, Onal M, Xiong J, Wang Y, Almeida M, Thostenson JD, Weinstein RS, Manolagas SC, O’Brien CA. Suppression of autophagy in osteocytes does not modify the adverse effects of glucocorticoids on cortical bone. Bone 75: 18–26, 2015.
277. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR. Multilineage potential of adult human mesenchymal stem cells. Science 284: 143–147, 1999.
278. Plotkin LI, Manolagas SC, Bellido T. Glucocorticoids induce osteocyte apoptosis by blocking focal adhesion kinase-mediated survival. Evidence for inside-out signaling leading to anoikis. J Biol Chem 282: 24120–24130, 2007.
279. Plotkin LI, Weinstein RS, Parfitt AM, Roberson PK, Manolagas SC, Bellido T. Prevention of osteocyte and osteoblast apoptosis by bisphosphonates and calcitonin. J Clin Invest 104: 1363–1374, 1999.
280. Polman JAE, Welten JE, Bosch DS, de Jonge RT, Balog J, van der Maarel SM, de Kloet ER, Datson NA. A genome-wide signature of glucocorticoid receptor binding in neuronal PC12 cells. BMC Neurosci 13: 118, 2012.
281. Pratt WB. The role of heat shock proteins in regulating the function, folding, and trafficking of the glucocorticoid receptor. J Biol Chem 268: 21455–21458, 1993.
282. Pratt WB, Silverstein AM, Galigniana MD. A model for the cytoplasmic trafficking of signalling proteins involving the hsp90-binding immunophilins and p50cdc37. Cell Signal 11: 839–851, 1999.
283. Pratt WB, Toft DO. Regulation of signaling protein function and trafficking by the hsp90/hsp70-based chaperone machinery. Exp Biol Med 228: 111–133, 2003.
284. Pratt WB, Toft DO. Steroid receptor interactions with heat shock protein and immunophilin chaperones. Endocr Rev 18: 306–360, 1997.
285. Presman DM, Ogara MF, Stortz M, Alvarez LD, Pooley JR, Schiltz RL, Grøntved L, Johnson TA, Mittelstadt PR, Ashwell JD, Ganesan S, Burton G, Levi V, Hager GL, Pecci A. Live cell imaging unveils multiple domain requirements for in vivo dimerization of the glucocorticoid receptor. PLoS Biol 12: e1001813, 2014.
286. Prummel MF, Wiersinga WM, Lips P, Sanders GT, Sauerwein HP. The course of biochemical parameters of bone turnover during treatment with corticosteroids. J Clin Endocrinol Metab 72: 382–386, 1991.
287. Rached MT, Kode A, Silva BC, Jung DY, Gray S, Ong H, Paik JH, DePinho RA, Kim JK, Karsenty G, Kousteni S. FoxO1 expression in osteoblasts regulates glucose homeostasis through regulation of osteocalcin in mice. J Clin Invest 120: 357–368, 2010.
288. Rauch A, Gossye V, Bracke D, Gevaert E, Jacques P, Van Beneden K, Vandooren B, Rauner M, Hofbauer LC, Haegeman G, Elewaut D, Tuckermann JP, De Bosscher K. An anti-inflammatory selective glucocorticoid receptor modulator preserves osteoblast differentiation. FASEB J 25: 1323–1332, 2011.
289. Rauch A, Seitz S, Baschant U, Schilling AF, Illing A, Stride B, Kirilov M, Mandic V, Takacz A, Schmidt-Ullrich R, Ostermay S, Schinke T, Spanbroek R, Zaiss MM, Angel PE, Lerner UH, David JP, Reichardt HM, Amling M, Schutz G, Tuckermann JP. Glucocorticoids suppress bone formation by attenuating osteoblast differentiation via the monomeric glucocorticoid receptor. Cell Metab 11: 517–531, 2010.
290. Rauner M, Goettsch C, Stein N, Thiele S, Bornhaeuser M, De Bosscher K, Haegeman G, Tuckermann J, Hofbauer LC. Dissociation of osteogenic and immunological effects by the selective glucocorticoid receptor agonist, compound A, in human bone marrow stromal cells. Endocrinology 152: 103–112, 2011.
291. Rauner M, Thiele S, Sinningen K, Winzer M, Salbach-Hirsch J, Gloe I, Peschke K, Haegeman G, Tuckermann JP, Hofbauer LC. Effects of the selective glucocorticoid receptor modulator compound A on bone metabolism and inflammation in male mice with collagen-induced arthritis. Endocrinology 154: 3719–3728, 2013.
292. Ray DW, Davis JR, White A, Clark AJ. Glucocorticoid receptor structure and function in glucocorticoid-resistant small cell lung carcinoma cells. Cancer Res 56: 3276–3280, 1996.
293. Raynauld JP, Buckland-Wright C, Ward R, Choquette D, Haraoui B, Martel-Pelletier J, Uthman I, Khy V, Tremblay JL, Bertrand C, Pelletier JP. Safety and efficacy of longterm intraarticular steroid injections in osteoarthritis of the knee: a randomized, double-blind, placebo-controlled trial. Arthritis Rheum 48: 370–377, 2003.
294. Reichardt HM, Kaestner KH, Tuckermann J, Kretz O, Wessely O, Bock R, Gass P, Schmid W, Herrlich P, Angel P, Schutz G. DNA binding of the glucocorticoid receptor is not essential for survival. Cell 93: 531–541, 1998.
295. Reichardt HM, Tuckermann JP, Gottlicher M, Vujic M, Weih F, Angel P, Herrlich P, Schutz G. Repression of inflammatory responses in the absence ofDNAbinding by the glucocorticoid receptor. EMBO J 20: 7168–7173, 2001.
296. Reid IR, Chapman GE, Fraser TR, Davies AD, Surus AS, Meyer J, Huq NL, Ibbertson HK. Low serum osteocalcin levels in glucocorticoid-treated asthmatics. J Clin Endocrinol Metab 62: 379–383, 1986.
297. Reily MM, Pantoja C, Hu X, Chinenov Y, Rogatsky I. The GRIP1:IRF3 interaction as a target for glucocorticoid receptor-mediated immunosuppression. The EMBO J 25: 108–117, 2006.
298. Rexin M, Busch W, Gehring U. Protein components of the nonactivated glucocorticoid receptor. J Biol Chem 266: 24601–24605, 1991.
299. Richardson DW, Dodge GR. Dose-dependent effects of corticosteroids on the expression of matrix-related genes in normal and cytokine-treated articular chondrocytes. Inflamm Res 52: 39–49, 2003.
300. Riggs DL, Roberts PJ, Chirillo SC, Cheung-Flynn J, Prapapanich V, Ratajczak T, Gaber R, Picard D, Smith DF. The Hsp90-binding peptidylprolyl isomerase FKBP52 potentiates glucocorticoid signaling in vivo. EMBO J 22: 1158–1167, 2003.
301. Ritchlin CT, Haas-Smith SA, Li P, Hicks DG, Schwarz EM. Mechanisms of TNF-alphaand RANKL-mediated osteoclastogenesis and bone resorption in psoriatic arthritis. J Clin Invest 111: 821–831, 2003.
302. Rivers C, Levy A, Hancock J, Lightman S, Norman M. Insertion of an amino acid in the DNA-binding domain of the glucocorticoid receptor as a result of alternative splicing. J Clin Endocrinol Metab 84: 4283–4286, 1999.
303. Robson H, Anderson E, Eden OB, Isaksson O, Shalet S. Chemotherapeutic agents used in the treatment of childhood malignancies have direct effects on growth plate chondrocyte proliferation. J Endocrinol 157: 225–235, 1998.
304. Rodriguez A, Griffiths-Jones S, Ashurst JL, Bradley A. Identification of Mammalian microRNA Host Genes and Transcription Units. Genome Res 14: 1902–1910, 2004.
305. Rogatsky I, Trowbridge JM, Garabedian MJ. Glucocorticoid receptor-mediated cell cycle arrest is achieved through distinct cell-specific transcriptional regulatory mechanisms. Mol Cell Biol 17: 3181–3193, 1997.
306. Rosen CJ, Bouxsein ML. Mechanisms of disease: is osteoporosis the obesity of bone? Nat Clin Pract Rheumatol 2: 35–43, 2006.
307. Rosenhagen MC, Soti C, Schmidt U, Wochnik GM, Hartl FU, Holsboer F, Young JC, Rein T. The heat shock protein 90-targeting drug cisplatin selectively inhibits steroid receptor activation. Mol Endocrinol 17: 1991–2001, 2003.
308. Saad MJ, Folli F, Kahn JA, Kahn CR. Modulation of insulin receptor, insulin receptor substrate-1, and phosphatidylinositol 3-kinase in liver and muscle of dexamethasonetreated rats. J Clin Invest 92: 2065–2072, 1993.
309. Sakakura M, Takebe K, Nakagawa S. Inhibition of luteinizing hormone secretion induced by synthetic LRH by long-term treatment with glucocorticoids in human subjects. J Clin Endocrinol Metab 40: 774–779, 1975.
310. Saldanha C, Tougas G, Grace E. Evidence for anti-inflammatory effect of normal circulating plasma cortisol. Clin Exp Rheumatol 4: 365–366, 1986.
311. Sanchez ER. Chaperoning steroidal physiology: lessons from mouse genetic models of Hsp90 and its cochaperones. Biochim Biophys Acta 1823: 722–729, 2012.
312. Sanchez ER, Meshinchi S, Tienrungroj W, Schlesinger MJ, Toft DO, Pratt WB. Relationship of the 90-kDa murine heat shock protein to the untransformed and transformed states of the L cell glucocorticoid receptor. J Biol Chem 262: 6986–6991, 1987.
313. Sanchez-Vega B, Krett N, Rosen ST, Gandhi V. Glucocorticoid receptor transcriptional isoforms and resistance in multiple myeloma cells. Mol Cancer Ther 5: 3062–3070, 2006.
314. Sato K, Suematsu A, Okamoto K, Yamaguchi A, Morishita Y, Kadono Y, Tanaka S, Kodama T, Akira S, Iwakura Y, Cua DJ, Takayanagi H. Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction. J Exp Med 203: 2673–2682, 2006.
315. Schacke H, Berger M, Rehwinkel H, Asadullah K. Selective glucocorticoid receptor agonists (SEGRAs): novel ligands with an improved therapeutic index. Molecular and Cell Endocrinol 275: 109–117, 2007.
316. Schacke H, Docke WD, Asadullah K. Mechanisms involved in the side effects of glucocorticoids. Pharmacol Ther 96: 23–43, 2002.
317. Scheller K, Sekeris CE, Krohne G, Hock R, Hansen IA, Scheer U. Localization of glucocorticoid hormone receptors in mitochondria of human cells. Eur J Cell Biol 79: 299–307, 2000.
318. Scherrer LC, Picard D, Massa E, Harmon JM, Simons SS Jr, Yamamoto KR, Pratt WB. Evidence that the hormone binding domain of steroid receptors confers hormonal control on chimeric proteins by determining their hormone-regulated binding to heat-shock protein 90. Biochemistry 32: 5381–5386, 1993.
319. Schiller BJ, Chodankar R, Watson LC, Stallcup MR, Yamamoto KR. Glucocorticoid receptor binds half sites as a monomer and regulates specific target genes. Genome Biol 15: 418, 2014.
320. Schlechter NL, Russell SM, Spencer EM, Nicoll CS. Evidence suggesting that the direct growth-promoting effect of growth hormone on cartilage in vivo is mediated by local production of somatomedin. Proc Natl Acad Sci USA 83: 7932–7934, 1986.
321. Schmidt KL, Pradhan DS, Shah AH, Charlier TD, Chin EH, Soma KK. Neurosteroids, immunosteroids, and the Balkanization of endocrinology. Gen Comp Endocrinol 157: 266–274, 2008.
322. Schrier L, Ferns SP, Barnes KM, Emons JA, Newman EI, Nilsson O, Baron J. Depletion of resting zone chondrocytes during growth plate senescence. J Endocrinol 189: 27–36, 2006.
323. Schubert N, Dudeck J, Liu P, Karutz A, Speier S, Maurer M, Tuckermann J, Dudeck A. Mast cell promotion of T cell-driven antigen-induced arthritis despite being dispensable for antibody-induced arthritis in which T cells are bypassed. Arthritis Rheumatol 67: 903–913, 2015.
324. Schweingruber N, Fischer HJ, Fischer L, van den Brandt J, Karabinskaya A, Labi V, Villunger A, Kretzschmar B, Huppke P, Simons M, Tuckermann JP, Flugel A, Luhder F, Reichardt HM. Chemokine-mediated redirection of T cells constitutes a critical mechanism of glucocorticoid therapy in autoimmune CNS responses. Acta Neuropathol 127: 713–729, 2014.
325. Seckl JR. 11Beta-hydroxysteroid dehydrogenases: changing glucocorticoid action. Curr Opin Pharmacol 4: 597–602, 2004.
326. Sekiya I, Koopman P, Tsuji K, Mertin S, Harley V, Yamada Y, Shinomiya K, Nifuji A, Noda M. Dexamethasone enhances SOX9 expression in chondrocytes. J Endocrinol 169: 573–579, 2001.
327. Sekiya I, Tsuji K, Koopman P, Watanabe H, Yamada Y, Shinomiya K, Nifuji A, Noda M. SOX9 enhances aggrecan gene promoter/enhancer activity and is up-regulated by retinoic acid in a cartilage-derived cell line, TC6. J Biol Chem 275: 10738–10744, 2000.
328. Shalhoub V, Conlon D, Tassinari M, Quinn C, Partridge N, Stein GS, Lian JB. Glucocorticoids promote development of the osteoblast phenotype by selectively modulating expression of cell growth and differentiation associated genes. J Cell Biochem 50: 425–440, 1992.
329. Shang J, Liu H, Zhou Y. Roles of microRNAs in prenatal chondrogenesis, postnatal chondrogenesis and cartilage-related diseases. J Cell Mol Med 17: 1515–1524, 2013.
330. Sher LB, Harrison JR, Adams DJ, Kream BE. Impaired cortical bone acquisition and osteoblast differentiation in mice with osteoblast-targeted disruption of glucocorticoid signaling. Calcif Tissue Int 79: 118–125, 2006.
331. Sher LB, Woitge HW, Adams DJ, Gronowicz GA, Krozowski Z, Harrison JR, Kream BE. Transgenic expression of 11beta-hydroxysteroid dehydrogenase type 2 in osteoblasts reveals an anabolic role for endogenous glucocorticoids in bone. Endocrinology 145: 922–929, 2004.
332. Shi C, Qi J, Huang P, Jiang M, Zhou Q, Zhou H, Kang H, Qian N, Yang Q, Guo L, Deng L. MicroRNA-17/20a inhibits glucocorticoid-induced osteoclast differentiation and function through targeting RANKL expression in osteoblast cells. Bone 68: 67–75, 2014.
333. Shi XM, Blair HC, Yang X, McDonald JM, Cao X. Tandem repeat of C/EBP binding sites mediates PPARgamma2 gene transcription in glucocorticoid-induced adipocyte differentiation. J Cell Biochem 76: 518–527, 2000.
334. Shimizu K, Nakajima A, Sudo K, Liu Y, Mizoroki A, Ikarashi T, Horai R, Kakuta S, Watanabe T, Iwakura Y. IL-1 receptor type 2 suppresses collagen-induced arthritis by inhibiting IL-1 signal on macrophages. J Immunol 194: 3156–3168, 2015.
335. Siebler T, Robson H, Shalet SM, Williams GR. Dexamethasone inhibits and thyroid hormone promotes differentiation of mouse chondrogenic ATDC5 cells. Bone 31: 457–464, 2002.
336. Siersbæk R, Nielsen R, John S, Sung MH, Baek S, Loft A, Hager GL, Mandrup S. Extensive chromatin remodelling and establishment of transcription factor ‘hotspots’ during early adipogenesis. EMBO J 30: 1459–1472, 2011.
337. Siersbaek R, Rabiee A, Nielsen R, Sidoli S, Traynor S, Loft A, La Cour Poulsen L, Rogowska-Wrzesinska A, Jensen ON, Mandrup S. Transcription factor cooperativity in early adipogenic hotspots and super-enhancers. Cell Rep 7: 1443–1455, 2014.
338. Silverman MN, Mukhopadhyay P, Belyavskaya E, Tonelli LH, Revenis BD, Doran JH, Ballard BE, Tam J, Pacher P, Sternberg EM. Glucocorticoid receptor dimerization is required for proper recovery of LPS-induced inflammation, sickness behavior and metabolism in mice. Mol Psychiatry 18: 1006–1017, 2013.
339. Simon D, Fernando C, Czernichow P, Prieur AM. Linear growth and final height in patients with systemic juvenile idiopathic arthritis treated with longterm glucocorticoids. J Rheumatol 29: 1296–1300, 2002.
340. Sims NA, Martin JT. Coupling signals between the osteoclast and osteoblast: how are messages transmitted between these temporary visitors to the bone surface? Front Endocrinol 6: 2015.
341. Sionov RV, Cohen O, Kfir S, Zilberman Y, Yefenof E. Role of mitochondrial glucocorticoid receptor in glucocorticoid-induced apoptosis. J Exp Med 203: 189–201, 2006.
342. Sivagurunathan S, Muir MM, Brennan TC, Seale JP, Mason RS. Influence of glucocorticoids on human osteoclast generation and activity. J Bone Miner Res 20: 390–398, 2005.
343. Skoner DP, Berger WE, Gawchik SM, Akbary A, Qiu C. Intranasal triamcinolone and growth velocity. Pediatrics 135: e348–356, 2015.
344. Smink JJ, Buchholz IM, Hamers N, van Tilburg CM, Christis C, Sakkers RJ, de Meer K, van Buul-Offers SC, Koedam JA. Short-term glucocorticoid treatment of piglets causes changes in growth plate morphology and angiogenesis. Osteoarthritis Cartilage 11: 864–871, 2003.
345. Smink JJ, Koedam JA, Koster JG, van Buul-Offers SC. Dexamethasone-induced growth inhibition of porcine growth plate chondrocytes is accompanied by changes in levels of IGF axis components. J Endocrinol 174: 343–352, 2002.
346. Smith DF, Toft DO. Steroid receptors and their associated proteins. Mol Endocrinol 7: 4–11, 1993.
347. Smith E, Coetzee GA, Frenkel B. Glucocorticoids inhibit cell cycle progression in differentiating osteoblasts via glycogen synthase kinase-3beta. J Biol Chem 277: 18191–18197, 2002.
348. Smith E, Frenkel B. Glucocorticoids inhibit the transcriptional activity of LEF/TCF in differentiating osteoblasts in a glycogen synthase kinase-3beta-dependent and -independent manner. J Biol Chem 280: 2388–2394, 2005.
349. Smith E, Redman RA, Logg CR, Coetzee GA, Kasahara N, Frenkel B. Glucocorticoids inhibit developmental stage-specific osteoblast cell cycle. Dissociation of cyclin Acyclin- dependent kinase 2 from E2F4-p130 complexes. J Biol Chem 275: 19992–20001, 2000.
350. Søe K, Delaissé JM. Glucocorticoids maintain human osteoclasts in the active mode of their resorption cycle. J Bone Miner Res 25: 2184–2192, 2010.
351. Spies CM, Straub RH, Cutolo M, Buttgereit F. Circadian rhythms in rheumatology: a glucocorticoid perspective. Arthritis Res Ther 16: S3, 2014.
352. Stahn C, Löwenberg M, Hommes DW, Buttgereit F. Molecular mechanisms of glucocorticoid action and selective glucocorticoid receptor agonists. Mol Cell Endocrinol 275: 71–78, 2007.
353. Starick SR, Ibn-Salem J, Jurk M, Hernandez C, Love MI, Chung HR, Vingron M, Thomas-Chollier M, Meijsing SH. ChIP-exo signal associated with DNA-binding motifs provide insights into the genomic binding of the glucocorticoid receptor and cooperating transcription factors. Genome Res 25: 825–835, 2015.
354. Steger DJ, Grant GR, Schupp M, Tomaru T, Lefterova MI, Schug J, Manduchi E, Stoeckert CJ, Lazar MA. Propagation of adipogenic signals through an epigenomic transition state. Genes Dev 24: 1035–1044, 2010.
355. Sternberg EM, Young WS, 3rd Bernardini R, Calogero AE, Chrousos GP, Gold PW, Wilder RL. A central nervous system defect in biosynthesis of corticotropin-releasing hormone is associated with susceptibility to streptococcal cell wall-induced arthritis in Lewis rats. Proc Natl Acad Sci USA 86: 4771–4775, 1989.
356. Stevens DA, Hasserjian RP, Robson H, Siebler T, Shalet SM, Williams GR. Thyroid hormones regulate hypertrophic chondrocyte differentiation and expression of parathyroid hormone-related peptide and its receptor during endochondral bone formation. J Bone Miner Res 15: 2431–2442, 2000.
357. Stöcklin E, Wissler M, Gouilleux F, Groner B. Functional interactions between Stat5 and the glucocorticoid receptor. Nature 383: 726–728, 1996.
358. Stove J, Schoniger R, Huch K, Brenner R, Gunther KP, Puhl W, Scharf HP. Effects of dexamethasone on proteoglycan content and gene expression of IL-1beta-stimulated osteoarthrotic chondrocytes in vitro. Acta Orthop Scand 73: 562–567, 2002.
359. Strapazzon G, De Toni L, Foresta C. Serum undercarboxylated osteocalcin was inversely associated with plasma glucose level and fat mass in type 2 diabetes mellitus. Osteoporos Int 22: 1643–1644, 2011.
360. Strehl C, Gaber T, Löwenberg M, Hommes DW, Verhaar AP, Schellmann S, Hahne M, Fangradt M, Wagegg M, Hoff P, Scheffold A, Spies CM, Burmester GR, Buttgereit F. Origin and functional activity of the membrane-bound glucocorticoid receptor. Arthritis Rheum 63: 3779–3788, 2011.
361. Surjit M, Ganti KP, Mukherji A, Ye T, Hua G, Metzger D, Li M, Chambon P. Widespread negative response elements mediate direct repression by agonist-liganded glucocorticoid receptor. Cell 145: 224–241, 2011.
362. Symmons DP, Bankhead CR, Harrison BJ, Brennan P, Barrett EM, Scott DG, Silman AJ. Blood transfusion, smoking, and obesity as risk factors for the development of rheumatoid arthritis: results from a primary care-based incident case-control study in Norfolk, England. Arthritis Rheum 40: 1955–1961, 1997.
363. Takahata M, Maher JR, Juneja SC, Inzana J, Xing L, Schwarz EM, Berger AJ, Awad HA. Mechanisms of bone fragility in a glucocorticoid-treated mouse model of rheumatoid arthritis: implications for insufficiency fracture risk. Arthritis Rheum 64: 3649–3659, 2012.
364. Takano T, Takigawa M, Suzuki F. Stimulation by glucocorticoids of the differentiated phenotype of chondrocytes and the proliferation of rabbit costal chondrocytes in culture. J Biochem 97: 1093–1100, 1985.
365. Taneja V, Mehra NK, Singh RR, Anand C, Malaviya AN. Immunogenetics of familial rheumatoid arthritis: a study of 41 multicase families. J Rheumatol 20: 253–258, 1993.
366. Tatsumi S, Ishii K, Amizuka N, Li M, Kobayashi T, Kohno K, Ito M, Takeshita S, Ikeda K. Targeted ablation of osteocytes induces osteoporosis with defective mechanotransduction. Cell Metab 5: 464–475, 2007.
367. Teitelbaum SL. Bone resorption by osteoclasts. Science 289: 1504–1508, 2000.
368. Teitelbaum SL, Ross FP. Genetic regulation of osteoclast development and function. Nat Rev Genet 4: 638–649, 2003.
369. Temiyasathit S, Jacobs CR. The osteocyte primary cilium and its role in bone mechanotransduction. Ann NY Acad Sci 1192: 422–428, 2010.
370. Thiele S, Ziegler N, Tsourdi E, De Bosscher K, Tuckermann JP, Hofbauer LC, Rauner M. Selective glucocorticoid receptor modulation maintains bone mineral density in mice. J Bone Miner Res 27: 2242–2250, 2012.
371. Thurman RE, Rynes E, Humbert R, Vierstra J, Maurano MT, Haugen E, Sheffield NC, Stergachis AB, Wang H, Vernot B, Garg K, Sandstrom R, Bates D, Canfield TK, Diegel M, Dunn D, Ebersol AK, Frum T, Giste E, Harding L, Johnson AK, Johnson EM, Kutyavin T, Lajoie B, Lee BK, Lee K, London D, Lotakis D, Neph S, Neri F, Nguyen ED, Reynolds AP, Roach V, Safi A, Sanchez ME, Sanyal A, Shafer A, Simon JM, Song L, Vong S, Weaver M, Zhang Z, Zhang Z, Lenhard B, Tewari M, Dorschner MO, Hansen RS, Navas PA, Stamatoyannopoulos G, Iyer VR, Lieb JD, Sunyaev SR, Akey JM, Sabo PJ, Kaul R, Furey TS, Dekker J, Crawford GE, Stamatoyannopoulos JA. The accessible chromatin landscape of the human genome. Nature 489: 75–82, 2012.
372. Todhunter RJ, Fubini SL, Wootton JA, Lust G. Effect of methylprednisolone acetate on proteoglycan and collagen metabolism of articular cartilage explants. J Rheumatol 23: 1207–1213, 1996.
373. Tomaszewska E, Dobrowolski P, Puzio I. Morphological changes of the cartilage and bone in newborn piglets evoked by experimentally induced glucocorticoid excess during pregnancy. J Anim Physiol Anim Nutr 97: 785–796, 2013.
374. Tomaszewska E, Dobrowolski P, Puzio I. Postnatal administration of 2-oxoglutaric acid improves the intestinal barrier affected by the prenatal action of dexamethasone in pigs. Nutrition 28: 190–196, 2012.
375. Trentham DE, Townes AS, Kang AH. Autoimmunity to type II collagen an experimental model of arthritis. J Exp Med 146: 857–868, 1977.
376. Tsompana M, Buck MJ. Chromatin accessibility: a window into the genome. Epigenetics Chromatin 7: 33, 2014.
377. Tu J, Henneicke H, Zhang Y, Stoner S, Cheng TL, Schindeler A, Chen D, Tuckermann J, Cooper MS, Seibel MJ, Zhou H. Disruption of glucocorticoid signaling in chondrocytes delays metaphyseal fracture healing but does not affect normal cartilage and bone development. Bone 69: 12–22, 2014.
378. Tuckermann JP, Kleiman A, Moriggl R, Spanbroek R, Neumann A, Illing A, Clausen BE, Stride B, Förster I, Habenicht AJR, Reichardt HM, Tronche F, Schmid W, Schütz G. Macrophages and neutrophils are the targets for immune suppression by glucocorticoids in contact allergy. J Clin Invest 117: 1381–1390, 2007.
379. Uhlenhaut NH, Barish GD, Yu RT, Downes M, Karunasiri M, Liddle C, Schwalie P, Hübner N, Evans RM. Insights into negative regulation by the glucocorticoid receptor from genome-wide profiling of inflammatory cistromes. Mol Cell 49: 158–171, 2013.
380. Urena P, Kubrusly M, Mannstadt M, Hruby M, Trinh MM, Silve C, Lacour B, Abou- Samra AB, Segre GV, Drueke T. The renal PTH/PTHrP receptor is down-regulated in rats with chronic renal failure. Kidney Int 45: 605–611, 1994.
381. Van Bezooijen RL, Farih-Sips HC, Papapoulos SE, Lowik CW. Interleukin-17: a new bone acting cytokine in vitro. J Bone Miner Res 14: 1513–1521, 1999.
382. Van Buul-Offers SC, Smink JJ, Gresnigt R, Hamers N, Koedam J, Karperien M. Thyroid hormone, but not parathyroid hormone, partially restores glucocorticoid-induced growth retardation. Pediatr Nephrol 20: 335–341, 2005.
383. Van Everdingen AA, Jacobs JW, Siewertsz Van Reesema DR, Bijlsma JW. Low-dose prednisone therapy for patients with early active rheumatoid arthritis: clinical efficacy, disease-modifying properties, and side effects: a randomized, double-blind, placebocontrolled clinical trial. Ann Intern Med 136: 1–12, 2002.
384. Van Gaalen FA, Toes RE, Ditzel HJ, Schaller M, Breedveld FC, Verweij CL, Huizinga TW. Association of autoantibodies to glucose-6-phosphate isomerase with extraarticular complications in rheumatoid arthritis. Arthritis Rheum 50: 395–399, 2004.
385. Van Raalte DH, Ouwens DM, Diamant M. Novel insights into glucocorticoid-mediated diabetogenic effects: towards expansion of therapeutic options? Eur J Clin Invest 39: 81–93, 2009.
386. Van Staa TP. The pathogenesis, epidemiology and management of glucocorticoidinduced osteoporosis. Calcif Tissue Int 79: 129–137, 2006.
387. Van Staa TP, Leufkens HG, Abenhaim L, Zhang B, Cooper C. Use of oral corticosteroids and risk of fractures. J Bone Miner Res 15: 993–1000, 2000.
388. Vande Berg BC, Malghem J, Lecouvet FE, Devogelaer JP, Maldague B, Houssiau FA. Fat conversion of femoral marrow in glucocorticoid-treated patients: a cross-sectional and longitudinal study with magnetic resonance imaging. Arthritis Rheum 42: 1405–1411, 1999.
389. Vandevyver S, Dejager L, Libert C. On the trail of the glucocorticoid receptor: into the nucleus and back. Traffic 13: 364–374, 2012.
390. Vanniasinghe AS, Manolios N, Schibeci S, Lakhiani C, Kamali-Sarvestani E, Sharma R, Kumar V, Moghaddam M, Ali M, Bender V. Targeting fibroblast-like synovial cells at sites of inflammation with peptide targeted liposomes results in inhibition of experimental arthritis. Clin Immunol 151: 43–54, 2014.
391. Vattakuzhi Y, Abraham SM, Freidin A, Clark AR, Horwood NJ. Dual-specificity phosphatase 1-null mice exhibit spontaneous osteolytic disease and enhanced inflammatory osteolysis in experimental arthritis. Arthritis Rheum 64: 2201–2210, 2012.
392. Vayssière BM, Dupont S, Choquart A, Petit F, Garcia T, Marchandeau C, Gronemeyer H, Resche-Rigon M. Synthetic glucocorticoids that dissociate transactivation and AP-1 transrepression exhibit antiinflammatory activity in vivo. Mol Endocrinol 11: 1245–1255, 1997.
393. Vermeer H, Hendriks-Stegeman BI, van der Burg B, van Buul-Offers SC, Jansen M. Glucocorticoid-induced increase in lymphocytic FKBP51 messenger ribonucleic acid expression: a potential marker for glucocorticoid sensitivity, potency, and bioavailability. J Clin Endocrinol Metab 88: 277–284, 2003.
394. Vernocchi S, Battello N, Schmitz S, Revets D, Billing AM, Turner JD, Muller CP. Membrane glucocorticoid receptor activation induces proteomic changes aligning with classical glucocorticoid effects. Mol Cell Proteomics 12: 1764–1779, 2013.
395. Vettorazzi S, Bode C, Dejager L, Frappart L, Shelest E, en CKs Tasdogan A, Reichardt HM, Libert C, Schneider M, Weih F, Uhlenhaut NH, David JP, ler MGa Kleiman A, Tuckermann JP. Glucocorticoids limit acute lung inflammation in concert with inflammatory stimuli by induction of SphK1. Nature Commun 6: 7796, 2015.
396. Voss TC, Schiltz RL, Sung MH, Yen PM, Stamatoyannopoulos JA, Biddie SC, Johnson TA, Miranda TB, John S, Hager GL. Dynamic exchange at regulatory elements during chromatin remodeling underlies assisted loading mechanism. Cell 146: 544–554, 2011.
397. Wake DJ, Walker BR. IIβ-Hydroxysteroid dehydrogenase type 1 in obesity and the metabolic syndrome. Mol Cell Endocrinol 215: 45–54, 2004.
398. Wallin R, Hutson SM. Dexamethasone stimulates vitamin K-dependent carboxylase activity in neonatal rats and cultured fetal hepatocytes. Pediatr Res 30: 281–285, 1991.
399. Walzer SM, Cetin E, Grübl-Barabas R, Sulzbacher I, Rueger B, Girsch W, Toegel S, Windhager R, Fischer MB. Vascularization of primary and secondary ossification centres in the human growth plate. BMC Dev Biol 14: 36, 2014.
400. Wang FS, Chuang PC, Chung PC, Lin CL, Chen MW, Ke HJ, Chang YH, Chen YS, Wu SL, Ko JY. MicroRNA-29a protects against glucocorticoid-induced bone loss and fragility in rats by orchestrating bone acquisition and resorption. Arthritis Rheum 65: 1530–1540, 2013.
401. Wang FS, Ko JY, Yeh DW, Ke HC, Wu HL. Modulation of Dickkopf-1 attenuates glucocorticoid induction of osteoblast apoptosis, adipocytic differentiation, and bone mass loss. Endocrinology 149: 1793–1801, 2008.
402. Wang FS, Lin CL, Chen YJ, Wang CJ, Yang KD, Huang YT, Sun YC, Huang HC. Secreted frizzled-related protein 1 modulates glucocorticoid attenuation of osteogenic activities and bone mass. Endocrinology 146: 2415–2423, 2005.
403. Wang J, Zhou J, Bondy CA. Igf1 promotes longitudinal bone growth by insulin-like actions augmenting chondrocyte hypertrophy. FASEB J 13: 1985–1990, 1999.
404. Wassenberg S, Rau R, Steinfeld P, Zeidler H. Very low-dose prednisolone in early rheumatoid arthritis retards radiographic progression over two years: a multicenter, double-blind, placebo-controlled trial. Arthritis Rheum 52: 3371–3380, 2005.
405. Wei J, Hanna T, Suda N, Karsenty G, Ducy P. Osteocalcin promotes beta-cell proliferation during development and adulthood through Gprc6a. Diabetes 63: 1021–1031, 2014.
406. Weinstein RS, Chen JR, Powers CC, Stewart SA, Landes RD, Bellido T, Jilka RL, Parfitt AM, Manolagas SC. Promotion of osteoclast survival and antagonism of bisphosphonate- induced osteoclast apoptosis by glucocorticoids. J Clin Invest 109: 1041–1048, 2002.
407. Weinstein RS, Jilka RL, Almeida M, Roberson PK, Manolagas SC. Intermittent parathyroid hormone administration counteracts the adverse effects of glucocorticoids on osteoblast and osteocyte viability, bone formation, and strength in mice. Endocrinology 151: 2641–2649, 2010.
408. Weinstein RS, Jilka RL, Parfitt AM, Manolagas SC. Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids. Potential mechanisms of their deleterious effects on bone. J Clin Invest 102: 274–282, 1998.
409. Weinstein RS, Wan C, Liu Q, Wang Y, Almeida M, O’brien CA, Thostenson J, Roberson PK, Boskey AL, Clemens TL, Manolagas SC. Endogenous glucocorticoids decrease skeletal angiogenesis, vascularity, hydration, and strength in 21-month-old mice. Aging Cell 9: 147–161, 2010.
410. Weinstein SP, Wilson CM, Pritsker A, Cushman SW. Dexamethasone inhibits insulinstimulated recruitment of GLUT4 to the cell surface in rat skeletal muscle. Metabolism 47: 3–6, 1998.
411. Weitoft T, Larsson A, Saxne T, Ronnblom L. Changes of cartilage and bone markers after intra-articular glucocorticoid treatment with and without postinjection rest in patients with rheumatoid arthritis. Ann Rheumatic Dis 64: 1750–1753, 2005.
412. Wellcome Trust Case Control. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447: 661–678, 2007.
413. Whyte WA, Orlando DA, Hnisz D, Abraham BJ, Lin CY, Kagey MH, Rahl PB, Lee TI, Young RA. Master transcription factors and mediator establish super-enhancers at key cell identity genes. Cell 153: 307–319, 2013.
414. Wipke BT, Allen PM. Essential role of neutrophils in the initiation and progression of a murine model of rheumatoid arthritis. J Immunol 167: 1601–1608, 2001.
415. Wochnik GM, Ruegg J, Abel GA, Schmidt U, Holsboer F, Rein T. FK506-binding proteins 51 and 52 differentially regulate dynein interaction and nuclear translocation of the glucocorticoid receptor in mammalian cells. J Biol Chem 280: 4609–4616, 2005.
416. Woods KA, Camacho-Hubner C, Savage MO, Clark AJ. Intrauterine growth retardation and postnatal growth failure associated with deletion of the insulin-like growth factor I gene. N Engl J Med 335: 1363–1367, 1996.
417. Worthley DL, Churchill M, Compton JT, Tailor Y, Rao M, Si Y, Levin D, Schwartz MG, Uygur A, Hayakawa Y, Gross S, Renz BW, Setlik W, Martinez AN, Chen X, Nizami S, Lee HG, Kang HP, Caldwell JM, Asfaha S, Westphalen CB, Graham T, Jin G, Nagar K, Wang H, Kheirbek MA, Kolhe A, Carpenter J, Glaire M, Nair A, Renders S, Manieri N, Muthupalani S, Fox JG, Reichert M, Giraud AS, Schwabe RF, Pradere JP, Walton K, Prakash A, Gumucio D, Rustgi AK, Stappenbeck TS, Friedman RA, Gershon MD, Sims P, Grikscheit T, Lee FY, Karsenty G, Mukherjee S, Wang TC. Gremlin 1 identifies a skeletal stem cell with bone, cartilage, and reticular stromal potential. Cell 160: 269–284, 2015.
418. Xia X, Kar R, Gluhak-Heinrich J, Yao W, Lane NE, Bonewald LF, Biswas SK, Lo WK, Jiang JX. Glucocorticoid-Induced Autophagy in Osteocytes. Bone Miner Res 25: 2479–2488, 2010.
419. Xing W, Hao L, Yang X, Li F, Huo H. Glucocorticoids induce apoptosis by inhibitingmicroRNA cluster miR1792 expression in chondrocytic cells. Mol Med Rep 10: 881–886, 2014.
420. Xiong J, Onal M, Jilka RL, Weinstein RS, Manolagas SC, O’Brien CA. Matrix-embedded cells control osteoclast formation. Nature Med 17: 1235–1241, 2011.
421. Yakar S, Rosen CJ, Beamer WG, Ackert-Bicknell CL, Wu Y, Liu JL, Ooi GT, Setser J, Frystyk J, Boisclair YR, LeRoith D. Circulating levels of IGF-I directly regulate bone growth and density. J Clin Invest 110: 771–781, 2002.
422. Yao W, Cheng Z, Busse C, Pham A, Nakamura MC, Lane NE. Glucocorticoid excess in mice results in early activation of osteoclastogenesis and adipogenesis and prolonged suppression of osteogenesis: a longitudinal study of gene expression in bone tissue from glucocorticoid-treated mice. Arthritis Rheum 58: 1674–1686, 2008.
423. Yao W, Dai W, Jiang JX, Lane NE. Glucocorticoids and osteocyte autophagy. Bone 54: 279–284, 2013.
424. Yavuz U, Sokucu S, Albayrak A, Ozturk K. Efficacy comparisons of the intraarticular steroidal agents in the patients with knee osteoarthritis. Rheumatol Int 32: 3391–3396, 2012.
425. Yeap BB, Chubb SA, Flicker L, McCaul KA, Ebeling PR, Beilby JP, Norman PE. Reduced serum total osteocalcin is associated with metabolic syndrome in older men via waist circumference, hyperglycemia, and triglyceride levels. Eur J Endocrinol 163: 265–272, 2010.
426. Yoshinaga SK, Peterson CL, Herskowitz I, Yamamoto KR. Roles of SWI1, SWI2, and SWI3 proteins for transcriptional enhancement by steroid receptors. Science 258: 1598–1604, 1992.
427. Zaidi M. Skeletal remodeling in health and disease. Nat Med 13: 791–801, 2007.
428. Zaman F, Chrysis D, Huntjens K, Chagin A, Takigawa M, Fadeel B, Savendahl L. Dexamethasone differentially regulates Bcl-2 family proteins in human proliferative chondrocytes: role of pro-apoptotic Bid. Toxicol Lett 224: 196–200, 2014.
429. Zaman F, Chrysis D, Huntjens K, Fadeel B, Sävendahl L. Ablation of the pro-apoptotic protein Bax protects mice from glucocorticoid-induced bone growth impairment. PLoS One 7: e33168, 2012.
430. Zhang W, Nuki G, Moskowitz RW, Abramson S, Altman RD, Arden NK, Bierma- Zeinstra S, Brandt KD, Croft P, Doherty M, Dougados M, Hochberg M, Hunter DJ, Kwoh K, Lohmander LS, Tugwell P. OARSI recommendations for the management of hip and knee osteoarthritis: part III: changes in evidence following systematic cumulative update of research published through January 2009. Osteoarthritis Cartilage 18: 476–499, 2010.
431. Zhang W, Yang N, Shi XM. Regulation of mesenchymal stem cell osteogenic differentiation by glucocorticoid-induced leucine zipper (GILZ). J Biol Chem 283: 4723–4729, 2008.
432. Zhou H, Mak W, Kalak R, Street J, Fong-Yee C, Zheng Y, Dunstan CR, Seibel MJ. Glucocorticoid-dependent Wnt signaling by mature osteoblasts is a key regulator of cranial skeletal development in mice. Development 136: 427–436, 2009.
433. Zhou H, Mak W, Zheng Y, Dunstan CR, Seibel MJ. Osteoblasts directly control lineage commitment of mesenchymal progenitor cells through Wnt signaling. J Biol Chem 283: 1936–1945, 2008.
434. Zhou Y, Xu BC, Maheshwari HG, He L, Reed M, Lozykowski M, Okada S, Cataldo L, Coschigamo K, Wagner TE, Baumann G, Kopchick JJ. A mammalian model for Laron syndrome produced by targeted disruption of the mouse growth hormone receptor/binding protein gene (the Laron?mouse). Proc Natl Acad Sci USA 94: 13215–13220, 1997.
435. Zou W, Greenblatt MB, Brady N, Lotinun S, Zhai B, de Rivera H, Singh A, Sun J, Gygi SP, Baron R, Glimcher LH, Jones DC. The microtubule-associated protein DCAMKL1 regulates osteoblast function via repression of Runx2. J Exp Med 210: 1793–1806, 2013.