Regulatory pathways associated with bone loss and bone marrow adiposity caused by aging, chemotherapy, glucocorticoid therapy and radiotherapy

American Journal of Stem Cells

Volumn 1, Issue 3, 2012, Pages 205-224

  Georgiou, Kristen R ^a   Hui, Susanta K ^b   Xian, Cory J ^a  

^a UNIVERSITY OF SOUTH AUSTRALIA   (Australia)

^b UNIVERSITY OF MINNESOTA   (United States)

Author keywords

Adipogenesis; Ageing; Bone marrow; Chemotherapy; Glucocorticoids; Mesenchymal stem cells; Osteogenesis; Oxidative stress; Radiotherapy; Wnt catenin signalling

Indexed keywords

ALKALINE PHOSPHATASE; BETA CATENIN; GLUCOCORTICOID; OSTEOPROTEGERIN; SECRETED FRIZZLED RELATED PROTEIN 1; SONIC HEDGEHOG PROTEIN; TRANSCRIPTION FACTOR RUNX1; WNT PROTEIN;

ADIPOGENESIS; AGING; BONE DENSITY; BONE DEVELOPMENT; BONE MARROW; CANCER CHEMOTHERAPY; CELL DIFFERENTIATION; CELL PROLIFERATION; GENE EXPRESSION; HUMAN; IMMUNOFLUORESCENCE; MICROENVIRONMENT; OSTEOLYSIS; OXIDATIVE STRESS; REVIEW; TREATMENT RESPONSE;

EID: 84895114448     PISSN: None     EISSN: 21604150     Source Type: Journal    
DOI: None     Document Type: Review

References (140)

1. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S and Marshak DR. Multilineage potential of adult human mesenchymal stem cells. Science 1999; 284: 143-147.
2. Fox JM, Chamberlain G, Ashton BA and Middleton J. Recent advances into the understanding of mesenchymal stem cell trafficking. Br J Haematol 2007; 137: 491-502.
3. Sacchetti B, Funari A, Michienzi S, Di Cesare S, Piersanti S, Saggio I, Tagliafico E, Ferrari S, Robey PG, Riminucci M and Bianco P. Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment. Cell 2007; 131: 324-336.
4. Zannettino AC, Paton S, Kortesidis A, Khor F, Itescu S and Gronthos S. Human mulipotential mesenchymal/stromal stem cells are derived from a discrete subpopulation of STRO1bright/CD34 /CD45(-)/glycophorin-A-bone marrow cells. Haematologica 2007; 92: 1707-1708.
5. Peled A, Petit I, Kollet O, Magid M, Ponomaryov T, Byk T, Nagler A, Ben-Hur H, Many A, Shultz L, Lider O, Alon R, Zipori D and Lapidot T. Dependence of human stem cell engraftment and repopulation of NOD/SCID mice on CXCR4. Science 1999; 283: 845-848.
6. Long M. Osteogenesis and Bone-Marrow-Derived cells. Blood cells, molecules and diseases 2001; 27: 677-690.
7. Kitazawa R, Mori K, Yamaguchi A, Kondo T and Kitazawa S. Modulation of mouse RANKL gene expression by Runx2 and vitamin D3. J Cell Biochem 2008; 105: 1289-1297.
8. Scheideler M, Elabd C, Zaragosi LE, Chiellini C, Hackl H, Sanchez-Cabo F, Yadav S, Duszka K, Friedl G, Papak C, Prokesch A, Windhager R, Ailhaud G, Dani C, Amri EZ and Trajanoski Z. Comparative transcriptomics of human multipotent stem cells during adipogenesis and osteoblastogenesis. BMC Genomics 2008; 9: 340.
9. Yoshida CA, Furuichi T, Fujita T, Fukuyama R, Kanatani N, Kobayashi S, Satake M, Takada K and Komori T. Core-binding factor beta interacts with Runx2 and is required for skeletal development. Nat Genet 2002; 32: 633-638.
10. Chaudhary LAH and Hruska K. Differential growth factor control of bone formation through osteoprogenitor differentiation. Bone 2004; 34: 402-411.
11. Bonewald LF and Johnson ML. Osteocytes, mechanosensing and Wnt signaling. Bone 2008; 42: 606-615.
12. Li HX, Luo X, Liu RX, Yang YJ and Yang GS. Roles of Wnt/beta-catenin signaling in adipogenic differentiation potential of adipose-derived mesenchymal stem cells. Mol Cell Endocrinol 2008; 291: 116-124.
13. Moerman EJ, Teng K, Lipschitz DA and LeckaCzernik B. Aging activates adipogenic and suppresses osteogenic programs in mesenchymal marrow stroma/stem cells: the role of PPARgamma2 transcription factor and TGF-beta/ BMP signaling pathways. Aging cell 2004; 3: 379-389.
14. Muruganandan S, Roman AA and Sinal CJ. Adipocyte differentiation of bone marrow-derived mesenchymal stem cells: cross talk with the osteoblastogenic program. Cellular and molecular life sciences: CMLS 2009; 66: 236-253.
15. Georgiou KR, Scherer MA, Fan CM, Cool JC, King TJ, Foster BK and Xian CJ. Methotrexate chemotherapy reduces osteogenesis but increases adipogenic potential in the bone marrow. Journal of cellular physiology 2012; 227: 909-918.
16. Kaplan RN, Psaila B and Lyden D. Niche-toniche migration of bone-marrow-derived cells. Trends Mol Med 2007; 13: 72-81.
17. Neiva K, Sun YX and Taichman RS. The role of osteoblasts in regulating hematopoietic stem cell activity and tumor metastasis. Braz J Med Biol Res 2005; 38: 1449-1454.
18. Arai F, Hira A, Ohmura M, Sato H, Matsuoka S, Takubo K, Ito K, Young Koh G and Suda T. Tie2/ Angiopoietin-1 Signaling Regulates Hematopoietic Stem Cell Quiescence in the Bone Marrow Niche. Cell 2004; 1118: 148-161.
19. Arai F and Suda T. Maintenance of quiescent hematopoietic stem cells in the osteoblastic niche. Ann N Y Acad Sci 2007; 1106: 41-53.
20. Wilson A and Trumpp A. Bone-marrow haematopoietic-stem-cell niches. Nat Rev Immunol 2006; 6: 93-106.
21. Li Z and Li L. Understanding hematopoietic stem-cell microenvironments. Trends Biochem Sci 2006; 31: 589-595.
22. Taichman RS. Blood and bone: two tissues whose fates are intertwined to create the hematopoietic stem-cell niche. Blood 2005; 105: 2631-2639.
23. Stier S, Ko Y, Forkert R, Lutz C, Neuhaus T, Grunewald E, Cheng T, Dombkowski D, Calvi LM, Rittling SR and Scadden DT. Osteopontin is a hematopoietic stem cell niche component that negatively regulates stem cell pool size. J Exp Med 2005; 201: 1781-1791.
24. Adams GB, Chabner KT, Alley IR, Olson DP, Szczepiorkowski ZM, Poznansky MC, Kos CH, Pollak MR, Brown EM and Scadden DT. Stem cell engraftment at the endosteal niche is specified by the calcium-sensing receptor. Nature 2006; 439: 599-603.
25. Naveiras O, Nardi V, Wenzel PL, Hauschka PV, Fahey F and Daley GQ. Bone-marrow adipocytes as negative regulators of the haematopoietic microenvironment. Nature 2009; 460: 259-263.
26. Belaid-Choucair Z, Lepelletier Y, Poncin G, Thiry A, Humblet C, Maachi M, Beaulieu A, Schneider E, Briquet A, Mineur P, Lambert C, Mendes-Da-Cruz D, Ahui ML, Asnafi V, Dy M, Boniver J, Nusgens BV, Hermine O and Defresne MP. Human bone marrow adipocytes block granulopoiesis through neuropilin-1-induced granulocyte colony-stimulating factor inhibition. Stem Cells 2008; 26: 1556-1564.
27. Takada I, Kouzmenko AP and Kato S. Wnt and PPARgamma signaling in osteoblastogenesis and adipogenesis. Nature reviews Rheumatology 2009; 5: 442-447.
28. Macsai CE, Foster BK and Xian CJ. Roles of Wnt signalling in bone growth, remodelling, skeletal disorders and fracture repair. J Cell Physiol 2008; 215: 578-587.
29. Bennett CN, Longo KA, Wright WS, Suva LJ, Lane TF, Hankenson KD and MacDougald OA. Regulation of osteoblastogenesis and bone mass by Wnt10b. Proc Natl Acad Sci U S A 2005; 102: 3324-3329.
30. Ross SE, Hemati N, Longo KA, Bennett CN, Lucas PC, Erickson RL and MacDougald OA. Inhibition of adipogenesis by Wnt signaling. Science 2000; 289: 950-953.
31. Cawthorn WP, Bree AJ, Yao Y, Du B, Hemati N, Martinez-Santibanez G and Macdougald OA. Wnt6, Wnt10a and Wnt10b inhibit adipogenesis and stimulate osteoblastogenesis through a beta-catenin-dependent mechanism. Bone 2012; 50: 477-489.
32. Zhou H, Mak W, Zheng Y, Dunstan CR and Seibel MJ. Osteoblasts directly control lineage commitment of mesenchymal progenitor cells through Wnt signaling. J Biol Chem 2008; 283: 1936-1945.
33. Chung SS, Lee JS, Kim M, Ahn BY, Jung HS, Lee HM, Kim JW and Park KS. Regulation of Wnt/ beta-Catenin Signaling by CCAAT/Enhancer Binding Protein beta During Adipogenesis. Obesity 2011.
34. Anastasilakis AD, Polyzos SA, Avramidis A, Toulis KA, Papatheodorou A and Terpos E. The effect of teriparatide on serum Dickkopf-1 levels in postmenopausal women with established osteoporosis. Clinical endocrinology 2010; 72: 752-757.
35. Taipaleenmaki H, Abdallah BM, Aldahmash A, Saamanen AM and Kassem M. Wnt signaling mediates the cross-talk between bone marrow derived pre-adipocytic and pre-osteoblastic cell populations. Exp Cell Res 2011; 317: 745-756.
36. Abdallah BM and Kassem M. New factors controlling the balance between osteoblastogenesis and adipogenesis. Bone 2012; 50: 540-545.
37. Bodine PV, Billiard J, Moran RA, Ponce-de-Leon H, McLarney S, Mangine A, Scrimo MJ, Bhat RA, Stauffer B, Green J, Stein GS, Lian JB and Komm BS. The Wnt antagonist secreted frizzled-related protein-1 controls osteoblast and osteocyte apoptosis. Journal of cellular biochemistry 2005; 96: 1212-1230.
38. Ingram WJ, Wicking CA, Grimmond SM, Forrest AR and Wainwright BJ. Novel genes regulated by Sonic Hedgehog in pluripotent mesenchymal cells. Oncogene 2002; 21: 8196-8205.
39. Rodda SJ and McMahon AP. Distinct roles for Hedgehog and canonical Wnt signaling in specification, differentiation and maintenance of osteoblast progenitors. Development 2006; 133: 3231-3244.
40. Spinella-Jaegle S, Rawadi G, Kawai S, Gallea S, Faucheu C, Mollat P, Courtois B, Bergaud B, Ramez V, Blanchet AM, Adelmant G, Baron R and Roman-Roman S. Sonic hedgehog increases the commitment of pluripotent mesenchymal cells into the osteoblastic lineage and abolishes adipocytic differentiation. Journal of cell science 2001; 114: 2085-2094.
41. He J, Sheng T, Stelter AA, Li C, Zhang X, Sinha M, Luxon BA and Xie J. Suppressing Wnt signaling by the hedgehog pathway through sFRP-1. The Journal of Biological Chemistry 2006; 281: 35598-35602.
42. Backesjo CM, Li Y, Lindgren U and Haldosen LA. Activation of Sirt1 decreases adipocyte formation during osteoblast differentiation of mesenchymal stem cells. J Bone Miner Res 2006; 21: 993-1002.
43. Backesjo CM, Li Y, Lindgren U and Haldosen LA. Activation of Sirt1 decreases adipocyte formation during osteoblast differentiation of mesenchymal stem cells. Cells Tissues Organs 2009; 189: 93-97.
44. Picard F, Kurtev M, Chung N, Topark-Ngarm A, Senawong T, Machado De Oliveira R, Leid M, McBurney MW and Guarente L. Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-gamma. Nature 2004; 429: 771-776.
45. Cohen-Kfir E, Artsi H, Levin A, Abramowitz E, Bajayo A, Gurt I, Zhong L, D'Urso A, Toiber D, Mostoslavsky R and Dresner-Pollak R. Sirt1 is a regulator of bone mass and a repressor of Sost encoding for sclerostin, a bone formation inhibitor. Endocrinology 2011; 152: 4514-4524.
46. Jin Q, Zhang F, Yan T, Liu Z, Wang C, Ge X and Zhai Q. C/EBPalpha regulates SIRT1 expression during adipogenesis. Cell research 2010; 20: 470-479.
47. Tang GY, Lv ZW, Tang RB, Liu Y, Peng YF, Li W and Cheng YS. Evaluation of MR spectroscopy and diffusion-weighted MRI in detecting bone marrow changes in postmenopausal women with osteoporosis. Clinical radiology 2010; 65: 377-381.
48. Griffith JF, Yeung DK, Antonio GE, Lee FK, Hong AW, Wong SY, Lau EM and Leung PC. Vertebral bone mineral density, marrow perfusion, and fat content in healthy men and men with osteoporosis: dynamic contrast-enhanced MR imaging and MR spectroscopy. Radiology 2005; 236: 945-951.
49. Yeung DK, Griffith JF, Antonio GE, Lee FK, Woo J and Leung PC. Osteoporosis is associated with increased marrow fat content and decreased marrow fat unsaturation: a proton MR spectroscopy study. Journal of magnetic resonance imaging: JMRI 2005; 22: 279-285.
50. Griffith JF, Yeung DK, Antonio GE, Wong SY, Kwok TC, Woo J and Leung PC. Vertebral marrow fat content and diffusion and perfusion indexes in women with varying bone density: MR evaluation. Radiology 2006; 241: 831-838.
51. Perrien DS, Akel NS, Dupont-Versteegden EE, Skinner RA, Siegel ER, Suva LJ and Gaddy D. Aging alters the skeletal response to disuse in the rat. American journal of physiology. Regulatory, integrative and comparative physiology 2007; 292: R988-996.
52. Duque G and Troen BR. Understanding the mechanisms of senile osteoporosis: new facts for a major geriatric syndrome. Journal of the American Geriatrics Society 2008; 56: 935-941.
53. Di Iorgi N, Rosol M, Mittelman SD and Gilsanz V. Reciprocal relation between marrow adiposity and the amount of bone in the axial and appendicular skeleton of young adults. The Journal of clinical endocrinology and metabolism 2008; 93: 2281-2286.
54. Astudillo P, Rios S, Pastenes L, Pino AM and Rodriguez JP. Increased adipogenesis of osteoporotic human-mesenchymal stem cells (MSCs) characterizes by impaired leptin action. Journal of cellular biochemistry 2008; 103: 1054-1065.
55. Kitazawa R, Kimble RB, Vannice JL, Kung VT and Pacifici R. Interleukin-1 receptor antagonist and tumor necrosis factor binding protein decrease osteoclast formation and bone resorption in ovariectomized mice. The Journal of clinical investigation 1994; 94: 2397-2406.
56. Zallone A. Direct and indirect estrogen actions on osteoblasts and osteoclasts. Annals of the New York Academy of Sciences 2006; 1068: 173-179.
57. Chen FP, Wang KC and Huang JD. Effect of estrogen on the activity and growth of human osteoclasts in vitro. Taiwanese journal of obstetrics & gynecology 2009; 48: 350-355.
58. Kim YY, Kim SH, Oh S, Sul OJ, Lee HY, Kim HJ, Kim SY and Choi HS. Increased fat due to estrogen deficiency induces bone loss by elevating monocyte chemoattractant protein-1 (MCP-1) production. Molecules and cells 2010; 29: 277-282.
59. Elbaz A, Rivas D and Duque G. Effect of estrogens on bone marrow adipogenesis and Sirt1 in aging C57BL/6J mice. Biogerontology 2009; 10: 747-755.
60. Stringer B, Waddington R, Houghton A, Stone M, Russell G and Foster G. Serum from postmenopausal women directs differentiation of human clonal osteoprogenitor cells from an osteoblastic toward an adipocytic phenotype. Calcified tissue international 2007; 80: 233-243.
61. Yalin S, Sagir O, Comelekoglu U, Berkoz M and Eroglu P. Strontium ranelate treatment improves oxidative damage in osteoporotic rat model. Pharmacological reports: PR 2012; 64: 396-402.
62. Chinn IK, Blackburn CC, Manley NR and Sempowski GD. Changes in primary lymphoid organs with aging. Seminars in immunology 2012.
63. Tang XL, Liu XJ, Tian Q and Zhang W. Dynamic Oxidative Stress and DNA Damage Induced by Oestrogen Deficiency and Protective Effects of Puerarin and 17beta-Oestradiol in Ovariectomized Rats. Basic & clinical pharmacology & toxicology 2012.
64. Muthusami S, Ramachandran I, Muthusamy B, Vasudevan G, Prabhu V, Subramaniam V, Jagadeesan A and Narasimhan S. Ovariectomy induces oxidative stress and impairs bone antioxidant system in adult rats. Clinica chimica acta; international journal of clinical chemistry 2005; 360: 81-86.
65. Halade GV, Rahman MM, Williams PJ and Fernandes G. Combination of conjugated linoleic acid with fish oil prevents age-associated bone marrow adiposity in C57Bl/6J mice. The Journal of nutritional biochemistry 2011; 22: 459-469.
66. Liu H, Yang X, Zhang Y, Dighe A, Li X and Cui Q. Fullerol antagonizes dexamethasone-induced oxidative stress and adipogenesis while enhancing osteogenesis in a cloned bone marrow mesenchymal stem cell. Journal of orthopaedic research: official publication of the Orthopaedic Research Society 2012; 30: 1051-1057.
67. Almeida M, Han L, Martin-Millan M, O'Brien CA and Manolagas SC. Oxidative stress antagonizes Wnt signaling in osteoblast precursors by diverting beta-catenin from T cell factorto forkhead box O-mediated transcription. The Journal of biological chemistry 2007; 282: 27298-27305.
68. Ambrogini E, Almeida M, Martin-Millan M, Paik JH, Depinho RA, Han L, Goellner J, Weinstein RS, Jilka RL, O'Brien CA and Manolagas SC. FoxO-mediated defense against oxidative stress in osteoblasts is indispensable for skeletal homeostasis in mice. Cell metabolism 2010; 11: 136-146.
69. Manolagas SC. From estrogen-centric to aging and oxidative stress: a revised perspective of the pathogenesis of osteoporosis. Endocrine reviews 2010; 31: 266-300.
70. Almeida M, Ambrogini E, Han L, Manolagas SC and Jilka RL. Increased lipid oxidation causes oxidative stress, increased peroxisome proliferator-activated receptor-gamma expression, and diminished pro-osteogenic Wnt signaling in the skeleton. The Journal of biological chemistry 2009; 284: 27438-27448.
71. Sharma C, Pradeep A, Wong L, Rana A and Rana B. Peroxisome proliferator-activated receptor gamma activation can regulate betacatenin levels via a proteasome-mediated and adenomatous polyposis coli-independent pathway. The Journal of biological chemistry 2004; 279: 35583-35594.
72. Chung SS, Lee JS, Kim M, Ahn BY, Jung HS, Lee HM, Kim JW and Park KS. Regulation of Wnt/ beta-catenin signaling by CCAAT/enhancer binding protein beta during adipogenesis. Obesity 2012; 20: 482-487.
73. Liu J, Wang H, Zuo Y and Farmer SR. Functional interaction between peroxisome proliferatoractivated receptor gamma and beta-catenin. Molecular and cellular biology 2006; 26: 5827-5837.
74. Paik JH, Ding Z, Narurkar R, Ramkissoon S, Muller F, Kamoun WS, Chae SS, Zheng H, Ying H, Mahoney J, Hiller D, Jiang S, Protopopov A, Wong WH, Chin L, Ligon KL and DePinho RA. FoxOs cooperatively regulate diverse pathways governing neural stem cell homeostasis. Cell stem cell 2009; 5: 540-553.
75. Terpos E, Christoulas D, Katodritou E, Bratengeier C, Gkotzamanidou M, Michalis E, Delimpasi S, Pouli A, Meletis J, Kastritis E, Zervas K and Dimopoulos MA. Elevated circulating sclerostin correlates with advanced disease features and abnormal bone remodeling in symptomatic myeloma: Reduction post-bortezomib monotherapy. International journal of cancer. Journal international du cancer 2011.
76. Caers J, Deleu S, Belaid Z, De Raeve H, Van Valckenborgh E, De Bruyne E, Defresne MP, Van Riet I, Van Camp B and Vanderkerken K. Neighboring adipocytes participate in the bone marrow microenvironment of multiple myeloma cells. Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 2007; 21: 1580-1584.
77. Reseland JE, Reppe S, Olstad OK, Hjorth-Hansen H, Brenne AT, Syversen U, Waage A and Iversen PO. Abnormal adipokine levels and leptin-induced changes in gene expression profiles in multiple myeloma. European journal of haematology 2009; 83: 460-470.
78. Saag KG, Shane E, Boonen S, Marin F, Donley DW, Taylor KA, Dalsky GP and Marcus R. Teriparatide or alendronate in glucocorticoid-induced osteoporosis. The New England journal of medicine 2007; 357: 2028-2039.
79. Yao W, Cheng Z, Busse C, Pham A, Nakamura MC and 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 and rheumatism 2008; 58: 1674-1686.
80. Butler JS, Queally JM, Devitt BM, Murray DW, Doran PP and O'Byrne JM. Silencing Dkk1 expression rescues dexamethasone-induced suppression of primary human osteoblast differentiation. BMC musculoskeletal disorders 2010; 11: 210.
81. Wang FS, Ko JY, Yeh DW, Ke HC and Wu HL. Modulation of Dickkopf-1 attenuates glucocorticoid induction of osteoblast apoptosis, adipocytic differentiation, and bone mass loss. Endocrinology 2008; 149: 1793-1801.
82. Kitajima M, Shigematsu M, Ogawa K, Sugihara H and Hotokebuchi T. Effects of glucocorticoid on adipocyte size in human bone marrow. Medical molecular morphology 2007; 40: 150-156.
83. Hung SH, Yeh CH, Huang HT, Wu P, Ho ML, Chen CH, Wang C, Chao D and Wang GJ. Pioglitazone and dexamethasone induce adipogenesis in D1 bone marrow stromal cell line, but not through the peroxisome proliferator-activated receptor-gamma pathway. Life sciences 2008; 82: 561-569.
84. Lin L, Dai SD and Fan GY. Glucocorticoid-induced differentiation of primary cultured bone marrow mesenchymal cells into adipocytes is antagonized by exogenous Runx2. APMIS: acta pathologica, microbiologica, et immunologica Scandinavica 2010; 118: 595-605.
85. Georgiou KR, Foster BK and Xian CJ. Damage and recovery of the bone marrow microenvironment induced by cancer chemotherapy potential regulatory role of chemokine CXCL12/receptor CXCR4 signalling. Curr Mol Med 2010; 10: 440-453.
86. Fan C, Georgiou KR, King TJ and Xian CJ. Methotrexate toxicity in growing long bones of young rats: a model for studying cancer chemotherapy-induced bone growth defects in children. Journal of biomedicine & biotechnology 2011; 2011: 903097.
87. Stevens SK, Moore SG and Kaplan ID. Early and late bone-marrow changes after irradiation: MR evaluation. AJR. American journal of roentgenology 1990; 154: 745-750.
88. Fogelman I, Blake GM, Blamey R, Palmer M, Sauerbrei W, Schumacher M, Serin D, Stewart A and Wilpshaar W. Bone mineral density in premenopausal women treated for node-positive early breast cancer with 2 years of goserelin or 6 months of cyclophosphamide, methotrexate and 5-fluorouracil (CMF). Osteoporosis international: a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 2003; 14: 1001-1006.
89. Buttiglieri S, Ruella M, Risso A, Spatola T, Silengo L, Avvedimento EV and Tarella C. The aging effect of chemotherapy on cultured human mesenchymal stem cells. Exp Hematol 2011; 39: 1171-1181.
90. King TJ, Georgiou KR, Cool JC, Scherer MA, Ang ES, Foster BK, Xu J and Xian CJ. Methotrexate Chemotherapy Promotes Osteoclast Formation in the Long Bone of Rats via Increased Pro-Inflammatory Cytokines and Enhanced NF-kappaB Activation. The American journal of pathology 2012.
91. Fan C, Cool JC, Scherer MA, Foster BK, Shandala T, Tapp H and Xian CJ. Damaging effects of chronic low-dose methotrexate usage on primary bone formation in young rats and potential protective effects of folinic acid supplementary treatment. Bone 2009; 44: 61-70.
92. Raghu Nadhanan R, Abimosleh SM, Su YW, Scherer MA, Howarth GS and Xian CJ. Dietary emu oil supplementation suppresses 5-fluorouracil chemotherapy-induced inflammation, osteoclast formation, and bone loss. American journal of physiology. Endocrinology and metabolism 2012; 302: E1440-1449.
93. Xian C, Cool J, Pyragius T and Foster B. Damage and recovery of the bone growth mechanism in young rats following 5-fluorouracil acute chemotherapy. Journal Cellular Biochemistry 2006; 99: 1688-1704.
94. Xian CJ, Cool JC, Scherer MA, Fan C and Foster BK. Folinic acid attenuates methotrexate chemotherapy-induced damages on bone growth mechanisms and pools of bone marrow stromal cells. J Cell Physiol 2008; 214: 777-785.
95. Georgiou KR, King TJ, Scherer MA, Zhou H, Foster BK and Xian CJ. Attenuated Wnt/betacatenin signalling mediates methotrexate chemotherapy-induced bone loss and marrow adiposity in rats. Bone 2012; 50: 1223-1233.
96. Georgiou KR, Scherer MA, Fan CM, Cool JC, King TJ, Foster BK and Xian CJ. Methotrexate chemotherapy reduces osteogenesis but increases adipogenesis potential in the bone marrow. J Cell Physiol 2011.
97. Vande Berg BC, Malghem J, Lecouvet FE, Devogelaer JP, Maldague B and Houssiau FA. Fat conversion of femoral marrow in glucocorticoid-treated patients: a cross-sectional and longitudinal study with magnetic resonance imaging. Arthritis and rheumatism 1999; 42: 1405-1411.
98. Nakamura-Ishizu A, Okuno Y, Omatsu Y, Okabe K, Morimoto J, Uede T, Nagasawa T, Suda T and Kubota Y. Extracellular matrix protein tenascin-C is required in the bone marrow microenvironment primed for hematopoietic regeneration. Blood 2012; 119: 5429-5437.
99. Zhang C, Lin J, Cui J, Li B, Liu C, Wang J, Gao F and Cai J. Radioprotection of bone marrow hematopoiesis by CpG-oligodeoxynucleotides administered to mice after total-body irradiation. Journal of radiation research 2011; 52: 828-833.
100. Zhang WC, Sun R, Zhang J and Tian Z. Recombinant human prolactin protects against irradiation-induced myelosuppression. Cellular & molecular immunology 2005; 2: 379-385.
101. Mitchell MJ and Logan PM. Radiation-induced changes in bone. Radiographics: a review publication of the Radiological Society of North America, Inc 1998; 18: 1125-1136; quiz 1242-1123.
102. Hui SK, Khalil A, Zhang Y, Coghill K, Le C, Dusenbery K, Froelich J, Yee D and Downs L. Longitudinal assessment of bone loss from diagnostic computed tomography scans in gynecologic cancer patients treated with chemotherapy and radiation. American journal of obstetrics and gynecology 2010; 203: 353 e351-357.
103. Baxter NN, Habermann EB, Tepper JE, Durham SB and Virnig BA. Risk of pelvic fractures in older women following pelvic irradiation. JAMA: the journal of the American Medical Association 2005; 294: 2587-2593.
104. Hui SK, Sharkey L, Kidder LS, Zhang Y, Fairchild G, Coghill K, Xian CJ and Yee D. The influence of therapeutic radiation on the patterns of bone marrow in ovary-intact and ovariectomized mice. PloS one 2012; 7: e42668.
105. Bianco P. Minireview: The stem cell next door: skeletal and hematopoietic stem cell "niches" in bone. Endocrinology 2011; 152: 2957-2962.
106. Despars G and St-Pierre Y. Bidirectional interactions between bone metabolism and hematopoiesis. Experimental hematology 2011; 39: 809-816.
107. Liu S, Hu P, Hou Y, Li P, Li X and Tian Q. The additive effect of mesenchymal stem cells and bone morphogenetic protein 2 on gamma-irradiated bone marrow in mice. Cell biochemistry and biophysics 2011; 61: 539-550.
108. Bernardo ME, Cometa AM and Locatelli F. Mesenchymal stromal cells: a novel and effective strategy for facilitating engraftment and accelerating hematopoietic recovery after transplantation? Bone marrow transplantation 2012; 47: 323-329.
109. Liang X, Su YP, Kong PY, Zeng DF, Chen XH, Peng XG, Zou ZM and Xu H. Human bone marrow mesenchymal stem cells expressing SDF-1 promote hematopoietic stem cell function of human mobilised peripheral blood CD34+ cells in vivo and in vitro. International journal of radiation biology 2010; 86: 230-237.
110. Harrison DE and Astle CM. Loss of stem cell repopulating ability upon transplantation. Effects of donor age, cell number, and transplantation procedure. The Journal of experimental medicine 1982; 156: 1767-1779.
111. Greenberger JS and Epperly M. Bone marrowderived stem cells and radiation response. Seminars in radiation oncology 2009; 19: 133-139.
112. Mussano F, Lee KJ, Zuk P, Tran L, Cacalano NA, Jewett A, Carossa S and Nishimura I. Differential effect of ionizing radiation exposure on multipotent and differentiation-restricted bone marrow mesenchymal stem cells. Journal of cellular biochemistry 2010; 111: 322-332.
113. Su W, Chen Y, Zeng W, Liu W and Sun H. Involvement of Wnt signaling in the injury of murine mesenchymal stem cells exposed to X-radiation. International journal of radiation biology 2012.
114. Li J, Kwong DL and Chan GC. The effects of various irradiation doses on the growth and differentiation of marrow-derived human mesenchymal stromal cells. Pediatric transplantation 2007; 11: 379-387.
115. Qiu J, Zhu G, Chen X, Shao C and Gu S. Combined effects of gamma-irradiation and cadmium exposures on osteoblasts in vitro. Environmental toxicology and pharmacology 2012; 33: 149-157.
116. Cachaco AS, Carvalho T, Santos AC, Igreja C, Fragoso R, Osorio C, Ferreira M, Serpa J, Correia S, Pinto-do OP and Dias S. TNF-alpha regulates the effects of irradiation in the mouse bone marrow microenvironment. PloS one 2010; 5: e8980.
117. Poole KE, van Bezooijen RL, Loveridge N, Hamersma H, Papapoulos SE, Lowik CW and Reeve J. Sclerostin is a delayed secreted product of osteocytes that inhibits bone formation. FASEB journal: official publication of the Federation of American Societies for Experimental Biology 2005; 19: 1842-1844.
118. Li J, Sarosi I, Cattley RC, Pretorius J, Asuncion F, Grisanti M, Morony S, Adamu S, Geng Z, Qiu W, Kostenuik P, Lacey DL, Simonet WS, Bolon B, Qian X, Shalhoub V, Ominsky MS, Zhu Ke H, Li X and Richards WG. Dkk1-mediated inhibition of Wnt signaling in bone results in osteopenia. Bone 2006; 39: 754-766.
119. Baron R and Rawadi G. Targeting the Wnt/beta-catenin pathway to regulate bone formation in the adult skeleton. Endocrinology 2007; 148: 2635-2643.
120. Hamersma H, Gardner J and Beighton P. The natural history of sclerosteosis. Clinical genetics 2003; 63: 192-197.
121. Ke HZ, Richards WG, Li X and Ominsky MS. Sclerostin and Dickkopf-1 as Therapeutic Targets in Bone Diseases. Endocrine reviews 2012.
122. Li X, Ominsky MS, Niu QT, Sun N, Daugherty B, D'Agostin D, Kurahara C, Gao Y, Cao J, Gong J, Asuncion F, Barrero M, Warmington K, Dwyer D, Stolina M, Morony S, Sarosi I, Kostenuik PJ, Lacey DL, Simonet WS, Ke HZ and Paszty C. Targeted deletion of the sclerostin gene in mice results in increased bone formation and bone strength. Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 2008; 23: 860-869.
123. Li X, Ominsky MS, Warmington KS, Morony S, Gong J, Cao J, Gao Y, Shalhoub V, Tipton B, Haldankar R, Chen Q, Winters A, Boone T, Geng Z, Niu QT, Ke HZ, Kostenuik PJ, Simonet WS, Lacey DL and Paszty C. Sclerostin antibody treatment increases bone formation, bone mass, and bone strength in a rat model of postmenopausal osteoporosis. Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 2009; 24: 578-588.
124. Li X, Warmington KS, Niu QT, Asuncion FJ, Barrero M, Grisanti M, Dwyer D, Stouch B, Thway TM, Stolina M, Ominsky MS, Kostenuik PJ, Simonet WS, Paszty C and Ke HZ. Inhibition of sclerostin by monoclonal antibody increases bone formation, bone mass, and bone strength in aged male rats. Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 2010; 25: 2647-2656.
125. Ominsky MS, Li C, Li X, Tan HL, Lee E, Barrero M, Asuncion FJ, Dwyer D, Han CY, Vlasseros F, Samadfam R, Jolette J, Smith SY, Stolina M, Lacey DL, Simonet WS, Paszty C, Li G and Ke HZ. Inhibition of sclerostin by monoclonal antibody enhances bone healing and improves bone density and strength of nonfractured bones. Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 2011; 26: 1012-1021.
126. Padhi D, Jang G, Stouch B, Fang L and Posvar E. Single-dose, placebo-controlled, randomized study of AMG 785, a sclerostin monoclonal antibody. Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 2011; 26: 19-26.
127. Glantschnig H, Hampton RA, Lu P, Zhao JZ, Vitelli S, Huang L, Haytko P, Cusick T, Ireland C, Jarantow SW, Ernst R, Wei N, Nantermet P, Scott KR, Fisher JE, Talamo F, Orsatti L, Reszka AA, Sandhu P, Kimmel D, Flores O, Strohl W, An Z and Wang F. Generation and selection of novel fully human monoclonal antibodies that neutralize Dickkopf-1 (DKK1) inhibitory function in vitro and increase bone mass in vivo. The Journal of biological chemistry 2010; 285: 40135-40147.
128. Glantschnig H, Scott K, Hampton R, Wei N, McCracken P, Nantermet P, Zhao JZ, Vitelli S, Huang L, Haytko P, Lu P, Fisher JE, Sandhu P, Cook J, Williams D, Strohl W, Flores O, Kimmel D, Wang F and An Z. A rate-limiting role for Dickkopf-1 in bone formation and the remediation of bone loss in mouse and primate models of postmenopausal osteoporosis by an experimental therapeutic antibody. The Journal of pharmacology and experimental therapeutics 2011; 338: 568-578.
129. Moore WJ, Kern JC, Bhat R, Commons TJ, Fukayama S, Goljer I, Krishnamurthy G, Magolda RL, Nogle L, Pitts K, Stauffer B, Trybulski EJ, Welmaker GS, Wilson M and Bodine PV. Modulation of Wnt signaling through inhibition of secreted frizzled-related protein I (sFRP-1) with N-substituted piperidinyl diphenylsulfonyl sulfonamides. Journal of medicinal chemistry 2009; 52: 105-116.
130. Bodine PV, Stauffer B, Ponce-de-Leon H, Bhat RA, Mangine A, Seestaller-Wehr LM, Moran RA, Billiard J, Fukayama S, Komm BS, Pitts K, Krishnamurthy G, Gopalsamy A, Shi M, Kern JC, Commons TJ, Woodworth RP, Wilson MA, Welmaker GS, Trybulski EJ and Moore WJ. A small molecule inhibitor of the Wnt antagonist secreted frizzled-related protein-1 stimulates bone formation. Bone 2009; 44: 1063-1068.
131. Reid IR. Anti-resorptive therapies for osteoporosis. Seminars in cell & developmental biology 2008; 19: 473-478.
132. Peng S, Liu XS, Wang T, Li Z, Zhou G, Luk KD, Guo XE and Lu WW. In vivo anabolic effect of strontium on trabecular bone was associated with increased osteoblastogenesis of bone marrow stromal cells. Journal of orthopaedic research: official publication of the Orthopaedic Research Society 2010; 28: 1208-1214.
133. Duque G, Li W, Adams M, Xu S and Phipps R. Effects of risedronate on bone marrow adipocytes in postmenopausal women. Osteoporosis international: a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 2011; 22: 1547-1553.
134. Fu L, Tang T, Miao Y, Zhang S, Qu Z and Dai K. Stimulation of osteogenic differentiation and inhibition of adipogenic differentiation in bone marrow stromal cells by alendronate via ERK and JNK activation. Bone 2008; 43: 40-47.
135. Jilka RL, Weinstein RS, Bellido T, Roberson P, Parfitt AM and Manolagas SC. Increased bone formation by prevention of osteoblast apoptosis with parathyroid hormone. The Journal of clinical investigation 1999; 104: 439-446.
136. Pettway GJ, Meganck JA, Koh AJ, Keller ET, Goldstein SA and McCauley LK. Parathyroid hormone mediates bone growth through the regulation of osteoblast proliferation and differentiation. Bone 2008; 42: 806-818.
137. Datta NS. Osteoporotic fracture and parathyroid hormone. World journal of orthopedics 2011; 2: 67-74.
138. Rickard DJ, Wang FL, Rodriguez-Rojas AM, Wu Z, Trice WJ, Hoffman SJ, Votta B, Stroup GB, Kumar S and Nuttall ME. Intermittent treatment with parathyroid hormone (PTH) as well as a non-peptide small molecule agonist of the PTH1 receptor inhibits adipocyte differentiation in human bone marrow stromal cells. Bone 2006; 39: 1361-1372.
139. Casado-Diaz A, Santiago-Mora R and Quesada JM. The Nand C-terminal domains of parathyroid hormone-related protein affect differently the osteogenic and adipogenic potential of human mesenchymal stem cells. Experimental & molecular medicine 2010; 42: 87-98.
140. Fischer-Posovszky P, Kukulus V, Tews D, Unterkircher T, Debatin KM, Fulda S and Wabitsch M. Resveratrol regulates human adipocyte number and function in a Sirt1-dependent manner. The American journal of clinical nutrition 2010; 92: 5-15.