Lessons from glucocorticoid receptor action in bone: New ways to avoid side effects of steroid therapy

Osteoimmunology: Interactions of the immune and skeletal systems

Volumn , Issue , 2013, Pages 31-48

  Rauch, Alexander ^a   Baschant, Ulrike ^a   Tuckermann, Jan ^a  

^a FRITZ LIPMANN INSTITUTE   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 84927910730     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1007/978-1-4614-5366-6_5     Document Type: Chapter

References (109)

1. Hench PS, Kendall EC, Slocumb CH, Polley HF (1950) Effects of cortisone acetate and pituitary ACTH on rheumatoid arthritis, rheumatic fever and certain other conditions. Arch Intern Med 85:545-566
2. Hoes JN, Jacobs JW, Buttgereit F, Bijlsma JW (2010) Current view of glucocorticoid cotherapy with DMARDs in rheumatoid arthritis. Nat Rev Rheumatol 6(12):693-702
3. Baschant U, Tuckermann J (2010) The role of the glucocorticoid receptor in in fl ammation and immunity. J Steroid Biochem Mol Biol 120(2-3):69-75
4. Nemoto T, Ohara-Nemoto Y, Denis M, Gustafsson JA (1990) The transformed glucocorticoid receptor has a lower steroid-binding affinity than the nontransformed receptor. Biochemistry 29(7):1880-1886
5. Davies TH, Ning YM, Sanchez ER (2002) A newfirst step in activation of steroid receptors: hormone-induced switching of FKBP51 and FKBP52 immunophilins. J Biol Chem 277(7): 4597-4600
6. Freedman ND, Yamamoto KR (2004) Importin 7 and importin alpha/importin beta are nuclear import receptors for the glucocorticoid receptor. Mol Biol Cell 15(5):2276-2286
7. Luisi BF, Xu WX, Otwinowski Z, Freedman LP, Yamamoto KR, Sigler PB (1991) Crystallographic analysis of the interaction of the glucocorticoid receptor with DNA. Nature 352(6335):497-505
8. Chandra V, Huang P, Hamuro Y, Raghuram S, Wang Y, Burris TP, Rastinejad F (2008) Structure of the intact PPAR-gamma-RXR-nuclear receptor complex on DNA. Nature 456(7220):350-356
9. Meijsing SH, Pufall MA, So AY, Bates DL, Chen L, Yamamoto KR (2009) DNA binding site sequence directs glucocorticoid receptor structure and activity. Science 324(5925):407-410
10. Stavreva DA, Wiench M, John S, Conway-Campbell BL, McKenna MA, Pooley JR, Johnson TA, Voss TC, Lightman SL, Hager GL (2009) Ultradian hormone stimulation induces glucocorticoid receptor-mediated pulses of gene transcription. Nat Cell Biol 11(9):1093-1102
11. Heck S, Kullmann M, Gast A, Ponta H, Rahmsdorf HJ, Herrlich P, Cato AC (1994) A distinct modulating domain in glucocorticoid receptor monomers in the repression of activity of the transcription factor AP-1. EMBO J 13(17):4087-4095
12. Heck S, Bender K, Kullmann M, Gottlicher M, Herrlich P, Cato AC (1997) I kappaB alphaindependent downregulation of NF-kappaB activity by glucocorticoid receptor. EMBO J 16(15):4698-4707
13. Reily MM, Pantoja C, Hu X, Chinenov Y, Rogatsky I (2006) The GRIP1:IRF3 interaction as a target for glucocorticoid receptor-mediated immunosuppression. EMBO J 25(1):108-117
14. Kassel O, Schneider S, Heilbock C, Litfin M, Gottlicher M, Herrlich P (2004) 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(20):2518-2528
15. He Y, Simons SS Jr (2007) STAMP, a novel predicted factor assisting TIF2 actions in glucocorticoid receptor-mediated induction and repression. Mol Cell Biol 27(4):1467-1485
16. De Bosscher K, Vanden Berghe W, Haegeman G (2001) Glucocorticoid repression of AP-1 is not mediated by competition for nuclear coactivators. Mol Endocrinol 15(2):219-227
17. Nissen RM, Yamamoto KR (2000) The glucocorticoid receptor inhibits NFkappaB by interfering with serine-2 phosphorylation of the RNA polymerase II carboxy-terminal domain. Genes Dev 14(18):2314-2329
18. Ogawa S, Lozach J, Benner C, Pascual G, Tangirala RK, Westin S, Hoffmann A, Subramaniam S, David M, Rosenfeld MG, Glass CK (2005) Molecular determinants of crosstalk between nuclear receptors and toll-like receptors. Cell 122(5):707-721
19. Flammer JR, Dobrovolna J, Kennedy MA, Chinenov Y, Glass CK, Ivashkiv LB, Rogatsky I (2010) The type I interferon signaling pathway is a target for glucocorticoid inhibition. Mol Cell Biol 30(19):4564-4574
20. De Bosscher K, Beck IM, Haegeman G (2010) Classic glucocorticoids versus non-steroidal glucocorticoid receptor modulators: survival of thefittest regulator of the immune system?. Brain Behav Immun 24(7):1035-1042
21. Belvisi MG, Wicks SL, Battram CH, Bottoms SE, Redford JE, Woodman P, Brown TJ, Webber SE, Foster ML (2001) Therapeutic benefit of a dissociated glucocorticoid and the relevance of in vitro separation of transrepression from transactivation activity. J Immunol 166(3):1975-1982
22. Coghlan MJ, Jacobson PB, Lane B, Nakane M, Lin CW, Elmore SW, Kym PR, Luly JR, Carter GW, Turner R, Tyree CM, Hu J, Elgort M, Rosen J, Miner JN (2003) A novel antiin fl ammatory maintains glucocorticoid efficacy with reduced side effects. Mol Endocrinol 17(5):860-869
23. De Bosscher K, Vanden Berghe W, Beck IM, Van Molle W, Hennuyer N, Hapgood J, Libert C, Staels B, Louw A, Haegeman G (2005) A fully dissociated compound of plant origin for in fl ammatory gene repression. Proc Natl Acad Sci USA 102(44):15827-15832
24. Lopez FJ, Ardecky RJ, Bebo B, Benbatoul K, De Grandpre L, Liu S, Leibowitz MD, Marschke K, Rosen J, Rungta D, Viveros HO, Yen WC, Zhi L, Negro-Vilar A, Miner JN (2008) LGD-5552, an antiin fl ammatory glucocorticoid receptor ligand with reduced side effects, in vivo. Endocrinology 149(5):2080-2089
25. Schacke H, Schottelius A, Docke WD, Strehlke P, Jaroch S, Schmees N, Rehwinkel H, Hennekes H, Asadullah K (2004) Dissociation of transactivation from transrepression by a selective glucocorticoid receptor agonist leads to separation of therapeutic effects from side effects. Proc Natl Acad Sci USA 101(1):227-232
26. Schacke H, Zollner TM, Docke WD, Rehwinkel H, Jaroch S, Skuballa W, Neuhaus R, May E, Zugel U, Asadullah K (2009) Characterization of ZK 245186, a novel, selective glucocorticoid receptor agonist for the topical treatment of in fl ammatory skin diseases. Br J Pharmacol 158(4):1088-1103
27. Wust S, Tischner D, John M, Tuckermann JP, Menzfeld C, Hanisch UK, van den Brandt J, Luhder F, Reichardt HM (2009) Therapeutic and adverse effects of a non-steroidal glucocorticoid receptor ligand in a mouse model of multiple sclerosis. PLoS One 4(12):e8202
28. van Loo G, Sze M, Bougarne N, Praet J, Mc Guire C, Ullrich A, Haegeman G, Prinz M, Beyaert R, De Bosscher K (2010) Antiin fl ammatory properties of a plant-derived nonsteroidal, dissociated glucocorticoid receptor modulator in experimental autoimmune encephalomyelitis. Mol Endocrinol 24(2):310-322
29. Dewint P, Gossye V, De Bosscher K, Vanden Berghe W, Van Beneden K, Deforce D, Van Calenbergh S, Muller-Ladner U, Vander Cruyssen B, Verbruggen G, Haegeman G, Elewaut D (2008) A plant-derived ligand favoring monomeric glucocorticoid receptor conformation with impaired transactivation potential attenuates collagen-induced arthritis. J Immunol 180(4):2608-2615
30. Humphrey EL, Williams JH, Davie MW, Marshall MJ (2006) Effects of dissociated glucocorticoids on OPG and RANKL in osteoblastic cells. Bone 38(5):652-661
31. Tronche F, Kellendonk C, Reichardt HM, Schutz G (1998) Genetic dissection of glucocorticoid receptor function in mice. Curr Opin Genet Dev 8(5):532-538
32. Tronche F, Kellendonk C, Kretz O, Gass P, Anlag K, Orban PC, Bock R, Klein R, Schutz G (1999) Disruption of the glucocorticoid receptor gene in the nervous system results in reduced anxiety. Nat Genet 23(1):99-103
33. Cole TJ, Blendy JA, Monaghan AP, Krieglstein K, Schmid W, Aguzzi A, Fantuzzi G, Hummler E, Unsicker K, Schütz G (1995) Targeted disruption of the glucocorticoid receptor gene blocks adrenergic chromaffin cell development and severely retards lung maturation. Genes Dev 9(13):1608-1621
34. Tuckermann JP, Kleiman A, Moriggl R, Spanbroek R, Neumann A, Illing A, Clausen BE, Stride B, Forster I, Habenicht AJ, Reichardt HM, Tronche F, Schmid W, Schutz G (2007) Macrophages and neutrophils are the targets for immune suppression by glucocorticoids in contact allergy. J Clin Invest 117(5):1381-1390
35. Bhattacharyya S, Brown DE, Brewer JA, Vogt SK, Muglia LJ (2007) Macrophage glucocorticoid receptors regulate Toll-like receptor-4-mediated in fl ammatory responses by selective inhibition of p38 MAP kinase. Blood 109(10):4313-4319
36. Wust S, van den Brandt J, Tischner D, Kleiman A, Tuckermann JP, Gold R, Luhder F, Reichardt HM (2008) Peripheral T cells are the therapeutic targets of glucocorticoids in experimental autoimmune encephalomyelitis. J Immunol 180(12):8434-8443
37. Reichardt HM, Kaestner KH, Tuckermann J, Kretz O, Wessely O, Bock R, Gass P, Schmid W, Herrlich P, Angel P, Schutz G (1998) DNA binding of the glucocorticoid receptor is not essential for survival. Cell 93(4):531-541
38. Reichardt HM, Tuckermann JP, Göttlicher M, Vujic M, Weih F, Angel P, Herrlich P, Schütz G (2001) Repression of in fl ammatory responses in the absence of DNA binding by the glucocorticoid receptor. EMBO J 20(24):7168-7173
39. Tuckermann JP, Reichardt HM, Arribas R, Richter KH, Schutz G, Angel P (1999) The DNA binding-independent function of the glucocorticoid receptor mediates repression of AP-1-dependent genes in skin. J Cell Biol 147(7):1365-1370
40. Ayroldi E, Migliorati G, Bruscoli S, Marchetti C, Zollo O, Cannarile L, D'Adamio F, Riccardi C (2001) Modulation of T-cell activation by the glucocorticoid-induced leucine zipper factor via inhibition of nuclear factor kappaB. Blood 98(3):743-753
41. Perretti M, D'Acquisto F (2009) Annexin A1 and glucocorticoids as effectors of the resolution of in fl ammation. Nat Rev Immunol 9(1):62-70
42. Kassel O, Sancono A, Kratzschmar J, Kreft B, Stassen M, Cato AC (2001) Glucocorticoids inhibit MAP kinase via increased expression and decreased degradation of MKP-1. EMBO J 20(24):7108-7116
43. Lasa M, Abraham SM, Boucheron C, Saklatvala J, Clark AR (2002) Dexamethasone causes sustained expression of mitogen-activated protein kinase (MAPK) phosphatase 1 and phosphatase-mediated inhibition of MAPK p38. Mol Cell Biol 22(22):7802-7811
44. Abraham SM, Lawrence T, Kleiman A, Warden P, Medghalchi M, Tuckermann J, Saklatvala J, Clark AR (2006) Antiin fl ammatory effects of dexamethasone are partly dependent on induction of dual specificity phosphatas 1. J Exp Med 203(8):1883-1889
45. Cushing H (1932) Further concerning a parasympathetic center in the interbrain: VII. The effect of intraventricularly-injected histamine. Proc Natl Acad Sci USA 18(7):500-510
46. 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 (1998) A UK Consensus Group on management of glucocorticoid-induced osteoporosis: an update. J Intern Med 244(4):271-292
47. Van Staa TP, Leufkens HG, Abenhaim L, Zhang B, Cooper C (2000) Use of oral corticosteroids and risk of fractures. J Bone Miner Res 15(6):993-1000
48. Dalle Carbonare L, Arlot ME, Chavassieux PM, Roux JP, Portero NR, Meunier PJ (2001) Comparison of trabecular bone microarchitecture and remodeling in glucocorticoid-induced and postmenopausal osteoporosis. J Bone Miner Res 16(1):97-103
49. Klein RG, Arnaud SB, Gallagher JC, Deluca HF, Riggs BL (1977) Intestinal calcium absorption in exogenous hypercortisonism. Role of 25-hydroxyvitamin D and corticosteroid dose. J Clin Invest 60(1):253-259
50. Nielsen HK, Thomsen K, Eriksen EF, Charles P, Storm T, Mosekilde L (1988) The effects of high-dose glucocorticoid administration on serum bone gamma carboxyglutamic acid-containing protein, serum alkaline phosphatase and vitamin D metabolites in normal subjects. Bone Miner 4(1):105-113
51. Mazziotti G, Angeli A, Bilezikian JP, Canalis E, Giustina A (2006) Glucocorticoid-induced osteoporosis: an update. Trends Endocrinol Metab 17(4):144-149
52. Parisien M, Silverberg SJ, Shane E, de la Cruz L, Lindsay R, Bilezikian JP, Dempster DW (1990) The histomorphometry of bone in primary hyperparathyroidism: preservation of cancellous bone structure. J Clin Endocrinol Metab 70(4):930-938
53. Sakakura M, Takebe K, Nakagawa S (1975) Inhibition of luteinizing hormone secretion induced by synthetic LRH by long-term treatment with glucocorticoids in human subjects. J Clin Endocrinol Metab 40(5):774-779
54. Hsueh AJ, Erickson GF (1978) Glucocorticoid inhibition of FSH-induced estrogen production in cultured rat granulosa cells. Steroids 32(5):639-648
55. Doerr P, Pirke KM (1976) Cortisol-induced suppression of plasma testosterone in normal adult males. J Clin Endocrinol Metab 43(3):622-629
56. Goulding A, Gold E (1988) Effects of chronic prednisolone treatment on bone resorption and bone composition in intact and ovariectomized rats and in ovariectomized rats receiving betaestradiol. Endocrinology 122(2):482-487
57. Hofbauer LC, Gori F, Riggs BL, Lacey DL, Dunstan CR, Spelsberg TC, Khosla S (1999) 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(10):4382-4389
58. Kondo T, Kitazawa R, Yamaguchi A, Kitazawa S (2008) Dexamethasone promotes osteoclastogenesis by inhibiting osteoprotegerin through multiple levels. J Cell Biochem 103(1):335-345
59. Hirano F, Kobayashi A, Maruyama N, Komura K, Okamoto K, Makino Y, Haneda M (2008) Parathyroid hormone and glucocorticoid cooperatively induce RANKL mRNA expression in osteoblasts through different mechanisms. In: European congress of endocrinology, vol 16. Berlin, p. 72
60. Pfeilschifter J, Chenu C, Bird A, Mundy GR, Roodman GD (1989) Interleukin-1 and tumor necrosis factor stimulate the formation of human osteoclastlike cells in vitro. J Bone Miner Res 4(1):113-118
61. Jilka RL, Hangoc G, Girasole G, Passeri G, Williams DC, Abrams JS, Boyce B, Broxmeyer H, Manolagas SC (1992) Increased osteoclast development after estrogen loss: mediation by interleukin-6. Science 257(5066):88-91
62. 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 (2010) Glucocorticoids suppress bone formation by attenuating osteoblast differentiation via the monomeric glucocorticoid receptor. Cell Metab 11(6):517-531
63. 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 (2011) An antiin fl ammatory selective glucocorticoid receptor modulator preserves osteoblast differentiation. FASEB J 25(4):1323-1332
64. Takuma A, Kaneda T, Sato T, Ninomiya S, Kumegawa M, Hakeda Y (2003) Dexamethasone enhances osteoclast formation synergistically with transforming growth factor-beta by stimulating the priming of osteoclast progenitors for differentiation into osteoclasts. J Biol Chem 278(45):44667-44674
65. Hofbauer LC, Zeitz U, Schoppet M, Skalicky M, Schuler C, Stolina M, Kostenuik PJ, Erben RG (2009) Prevention of glucocorticoid-induced bone loss in mice by inhibition of RANKL. Arthritis Rheum 60(5):1427-1437
66. Jia D, O'Brien CA, Stewart SA, Manolagas SC, Weinstein RS (2006) Glucocorticoids act directly on osteoclasts to increase their life span and reduce bone density. Endocrinology 147(12):5592-5599
67. Kim HJ, Zhao H, Kitaura H, Bhattacharyya S, Brewer JA, Muglia LJ, Ross FP, Teitelbaum SL (2006) Glucocorticoids suppress bone formation via the osteoclast. J Clin Invest 116(8):2152-2160
68. Smith E, Redman RA, Logg CR, Coetzee GA, Kasahara N, Frenkel B (2000) Glucocorticoids inhibit developmental stage-specific osteoblast cell cycle. Dissociation of cyclin A-cyclindependent kinase 2 from E2F4-p130 complexes. J Biol Chem 275(26):19992-20001
69. Smith E, Coetzee GA, Frenkel B (2002) Glucocorticoids inhibit cell cycle progression in differentiating osteoblasts via glycogen synthase kinase-3beta. J Biol Chem 277(20):18191-18197
70. Smith E, Frenkel B (2005) 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(3):2388-2394
71. Ohnaka K, Taniguchi H, Kawate H, Nawata H, Takayanagi R (2004) Glucocorticoid enhances the expression of dickkopf-1 in human osteoblasts: novel mechanism of glucocorticoidinduced osteoporosis. Biochem Biophys Res Commun 318(1):259-264
72. Butler JS, Queally JM, Devitt BM, Murray DW, Doran PP, O'Byrne JM (2010) Silencing Dkk1 expression rescues dexamethasone-induced suppression of primary human osteoblast differentiation. BMC Musculoskelet Disord 11:210
73. Horsch K, de Wet H, Schuurmans MM, Allie-Reid F, Cato AC, Cunningham J, Burrin JM, Hough FS, Hulley PA (2007) Mitogen-activated protein kinase phosphatase 1/dual specificity phosphatase 1 mediates glucocorticoid inhibition of osteoblast proliferation. Mol Endocrinol 21(12):2929-2940
74. Weinstein RS, Jilka RL, Parfitt AM, Manolagas SC (1998) 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(2):274-282
75. Plotkin LI, Weinstein RS, Parfitt AM, Roberson PK, Manolagas SC, Bellido T (1999) Prevention of osteocyte and osteoblast apoptosis by bisphosphonates and calcitonin. J Clin Invest 104(10):1363-1374
76. Plotkin LI, Mathov I, Aguirre JI, Parfitt AM, Manolagas SC, Bellido T (2005) Mechanical stimulation prevents osteocyte apoptosis: requirement of integrins, Src kinases, and ERKs. Am J Physiol Cell Physiol 289(3):C633-C643
77. Bellido T (2010) Antagonistic interplay between mechanical forces and glucocorticoids in bone: a tale of kinases. J Cell Biochem 111(1):1-6
78. Plotkin LI, Manolagas SC, Bellido T (2007) Glucocorticoids induce osteocyte apoptosis by blocking focal adhesion kinase-mediated survival: evidence for inside-out signaling leading to anoikis. J Biol Chem 282(33):24120-24130
79. Xiong W, Parsons JT (1997) Induction of apoptosis after expression of PYK2, a tyrosine kinase structurally related to focal adhesion kinase. J Cell Biol 139(2):529-539
80. Hong D, Chen HX, Yu HQ, Wang C, Deng HT, Lian QQ, Ge RS (2010) Quantitative proteomic analysis of dexamethasone-induced effects on osteoblast differentiation, proliferation, and apoptosis in MC3T3-E1 cells using SILAC. Osteoporos Int 22(7):2175-2186
81. O'Brien CA, Jia D, Plotkin LI, Bellido T, Powers CC, Stewart SA, Manolagas SC, Weinstein RS (2004) Glucocorticoids act directly on osteoblasts and osteocytes to induce their apoptosis and reduce bone formation and strength. Endocrinology 145(4):1835-1841
82. Cheng SL, Yang JW, Rifas L, Zhang SF, Avioli LV (1994) Differentiation of human bone marrow osteogenic stromal cells in vitro: induction of the osteoblast phenotype by dexamethasone. Endocrinology 134(1):277-286
83. Bellows CG, Aubin JE, Heersche JN (1987) Physiological concentrations of glucocorticoids stimulate formation of bone nodules from isolated rat calvaria cells in vitro. Endocrinology 121(6):1985-1992
84. Eijken M, Koedam M, van Driel M, Buurman CJ, Pols HA, van Leeuwen JP (2006) The essential role of glucocorticoids for proper human osteoblast differentiation and matrix mineralization. Mol Cell Endocrinol 248(1-2):87-93
85. Sher LB, Woitge HW, Adams DJ, Gronowicz GA, Krozowski Z, Harrison JR, Kream BE (2004) Transgenic expression of 11beta-hydroxysteroid dehydrogenase type 2 in osteoblasts reveals an anabolic role for endogenous glucocorticoids in bone. Endocrinology 145(2): 922-929
86. Sher LB, Harrison JR, Adams DJ, Kream BE (2006) Impaired cortical bone acquisition and osteoblast differentiation in mice with osteoblast-targeted disruption of glucocorticoid signaling. Calcif Tissue Int 79(2):118-125
87. Chang DJ, Ji C, Kim KK, Casinghino S, McCarthy TL, Centrella M (1998) Reduction in transforming growth factor beta receptor I expression and transcription factor CBFa1 on bone cells by glucocorticoid. J Biol Chem 273(9):4892-4896
88. Komori T, Yagi H, Nomura S, Yamaguchi A, Sasaki K, Deguchi K, Shimizu Y, Bronson RT, Gao YH, Inada M, Sato M, Okamoto R, Kitamura Y, Yoshiki S, Kishimoto T (1997) Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell 89(5):755-764
89. Delany AM, Gabbitas BY, Canalis E (1995) Cortisol downregulates osteoblast alpha 1 (I) procollagen mRNA by transcriptional and posttranscriptional mechanisms. J Cell Biochem 57(3):488-494
90. Centrella M, McCarthy TL, Canalis E (1991) Glucocorticoid regulation of transforming growth factor beta 1 activity and binding in osteoblast-enriched cultures from fetal rat bone. Mol Cell Biol 11(9):4490-4496
91. Luppen CA, Chandler RL, Noh T, Mortlock DP, Frenkel B (2008) BMP-2 vs. BMP-4 expression and activity in glucocorticoid-arrested MC3T3-E1 osteoblasts: Smad signaling, not alkaline phosphatase activity, predicts rescue of mineralization. Growth Factors 26(4):226-237
92. Luppen CA, Leclerc N, Noh T, Barski A, Khokhar A, Boskey AL, Smith E, Frenkel B (2003) Brief bone morphogenetic protein 2 treatment of glucocorticoid-inhibited MC3T3-E1 osteoblasts rescues commitment-associated cell cycle and mineralization without alteration of Runx2. J Biol Chem 278(45):44995-45003
93. Leclerc N, Luppen CA, Ho VV, Nagpal S, Hacia JG, Smith E, Frenkel B (2004) Gene expression profiling of glucocorticoid-inhibited osteoblasts. J Mol Endocrinol 33(1):175-193
94. Levi G, Topilko P, Schneider-Maunoury S, Lasagna M, Mantero S, Cancedda R, Charnay P (1996) Defective bone formation in Krox-20 mutant mice. Development 122(1):113-120
95. Seitanidou T, Schneider-Maunoury S, Desmarquet C, Wilkinson DG, Charnay P (1997) Krox-20 is a key regulator of rhombomere-specific gene expression in the developing hindbrain. Mech Dev 65(1-2):31-42
96. Fainsod A, Deissler K, Yelin R, Marom K, Epstein M, Pillemer G, Steinbeisser H, Blum M (1997) The dorsalizing and neural inducing gene follistatin is an antagonist of BMP-4. Mech Dev 63(1):39-50
97. Delany AM, Rydziel S, Canalis E (1996) Autocrine down-regulation of collagenase-3 in rat bone cell cultures by insulin-like growth factors. Endocrinology 137(11):4665-4670
98. Canalis E, Centrella M, Burch W, McCarthy TL (1989) Insulin-like growth factor I mediates selective anabolic effects of parathyroid hormone in bone cultures. J Clin Invest 83(1): 60-65
99. Delany AM, Durant D, Canalis E (2001) Glucocorticoid suppression of IGF I transcription in osteoblasts. Mol Endocrinol 15(10):1781-1789
100. Gabbitas B, Pash JM, Delany AM, Canalis E (1996) Cortisol inhibits the synthesis of insulinlike growth factor-binding protein-5 in bone cell cultures by transcriptional mechanisms. J Biol Chem 271(15):9033-9038
101. Devlin RD, Du Z, Buccilli V, Jorgetti V, Canalis E (2002) Transgenic mice overexpressing insulin-like growth factor binding protein-5 display transiently decreased osteoblastic function and osteopenia. Endocrinology 143(10):3955-3962
102. Rosen CJ, Bouxsein ML (2006) Mechanisms of disease: is osteoporosis the obesity of bone?. Nat Clin Pract Rheumatol 2(1):35-43
103. Rosen CJ, Ackert-Bicknell C, Beamer WG, Nelson T, Adamo M, Cohen P, Bouxsein ML, Horowitz MC (2005) Allelic differences in a quantitative trait locus affecting insulin-like growth factor-I impact skeletal acquisition and body composition. Pediatr Nephrol 20(3):255-260
104. Wehrli FW, Hopkins JA, Hwang SN, Song HK, Snyder PJ, Haddad JG (2000) Cross-sectional study of osteopenia with quantitative MR imaging and bone densitometry. Radiology 217(2):527-538
105. Asada M, Rauch A, Shimizu H, Maruyama H, Miyaki S, Shibamori M, Kawasome H, Ishiyama H, Tuckermann J, Asahara H (2010) DNA binding-dependent glucocorticoid receptor activity promotes adipogenesis via Kruppel-like factor 15 gene expression. Lab Invest 91(2):203-215
106. Takeuchi Y, Watanabe S, Ishii G, Takeda S, Nakayama K, Fukumoto S, Kaneta Y, Inoue D, Matsumoto T, Harigaya K, Fujita T (2002) Interleukin-11 as a stimulatory factor for bone formation prevents bone loss with advancing age in mice. J Biol Chem 277(50): 49011-49018
107. Itoh S, Udagawa N, Takahashi N, Yoshitake F, Narita H, Ebisu S, Ishihara K (2006) A critical role for interleukin-6 family-mediated Stat3 activation in osteoblast differentiation and bone formation. Bone 39(3):505-512
108. Sims NA, Jenkins BJ, Nakamura A, Quinn JM, Li R, Gillespie MT, Ernst M, Robb L, Martin TJ (2005) Interleukin-11 receptor signaling is required for normal bone remodeling. J Bone Miner Res 20(7):1093-1102
109. Rauner M, Goettsch C, Stein N, Thiele S, Bornhaeuser M, De Bosscher K, Haegeman G, Tuckermann J, Hofbauer LC (2011) Dissociation of osteogenic and immunological effects by the selective glucocorticoid receptor agonist, compound a, in human bone marrow stromal cells. Endocrinology 152(1):103-112