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PPAR Research
Volume 2006, Article ID 27489, 9 pages
http://dx.doi.org/10.1155/PPAR/2006/27489
Review Article

Resolving the Two “Bony” Faces of PPAR-γ

1Department of Geriatrics, Reynolds Institute on Aging, University of Arkansas for Medical Sciences, 629 Jack Stephens Drive, Little Rock, AR 72205, USA
2Department of Orthopaedic Surgery, Center for Orthopaedic Research, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA

Received 31 May 2006; Revised 18 July 2006; Accepted 19 July 2006

Copyright © 2006 Beata Lecka-Czernik and Larry J. Suva. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. P G Robey and P Bianco, “Cellular mechanisms of age-related bone loss,” in The Aging Skeleton, C GJ Rosen and J P Bilezikian, Eds., pp. 145–157, Academic Press, San Diego, Califf, 1999. View at Google Scholar
  2. J M Gimble, C E Robinson, X Wu, and K A Kelly, “The function of adipocytes in the bone marrow stroma: an update,” Bone, vol. 19, no. suppl 5, pp. 421–428, 1996. View at Publisher · View at Google Scholar
  3. J M Gimble, S Zvonic, Z E Floyd, M Kassem, and M E Nuttall, “Playing with bone and fat,” Journal of Cellular Biochemistry, vol. 98, no. 2, pp. 251–266, 2006. View at Publisher · View at Google Scholar
  4. B Lecka-Czernik, E J Moerman, D F Grant, J M Lehmann, S C Manolagas, and R L Jilka, “Divergent effects of selective peroxisome proliferator-activated receptor-γ2 ligands on adipocyte versus osteoblast differentiation,” Endocrinology, vol. 143, no. 6, pp. 2376–2384, 2002. View at Publisher · View at Google Scholar
  5. O P Lazarenko, S O Rzonca, L J Suva, and B Lecka-Czernik, “Netoglitazone is a PPAR-gamma ligand with selective effects on bone and fat,” Bone, vol. 38, no. 1, pp. 74–84, 2006. View at Publisher · View at Google Scholar
  6. Y Jiang, B N Jahagirdar, R L Reinhardt et al., “Pluripotency of mesenchymal stem cells derived from adult marrow,” Nature, vol. 418, no. 6893, pp. 41–49, 2002. View at Publisher · View at Google Scholar
  7. P Bianco, M Riminucci, S Gronthos, and P G Robey, “Bone marrow stromal stem cells: nature, biology, and potential applications,” Stem Cells, vol. 19, no. 3, pp. 180–192, 2001. View at Publisher · View at Google Scholar
  8. J E Aubin, “Regulation of osteoblast formation and function,” Reviews in Endocrine and Metabolic Disorders, vol. 2, no. 1, pp. 81–94, 2001. View at Publisher · View at Google Scholar
  9. B Lecka-Czernik, I Gubrij, E J Moerman et al., “Inhibition of Osf2/Cbfa1 expression and terminal osteoblast differentiation by PPAR?2,” Journal of Cellular Biochemistry, vol. 74, no. 3, pp. 357–371, 1999. View at Publisher · View at Google Scholar
  10. E J Moerman, K Teng, D A Lipschitz, and B Lecka-Czernik, “Aging activates adipogenic and suppresses osteogenic programs in mesenchymal marrow stroma/stem cells: the role of PPAR-γ2 transcription factor and TGF-β/BMP signaling pathways,” Aging Cell, vol. 3, no. 6, pp. 379–389, 2004. View at Publisher · View at Google Scholar
  11. K Stenderup, J Justesen, C Clausen, and M Kassem, “Aging is associated with decreased maximal life span and accelerated senescence of bone marrow stromal cells,” Bone, vol. 33, no. 6, pp. 919–926, 2003. View at Publisher · View at Google Scholar
  12. B M Abdallah, M Haack-Sørensen, T Fink, and M Kassem, “Inhibition of osteoblast differentiation but not adipocyte differentiation of mesenchymal stem cells by sera obtained from aged females,” Bone, vol. 39, no. 1, pp. 181–188, 2006. View at Publisher · View at Google Scholar
  13. F P Ross and S L Teitelbaum, “αvβ3 and macrophage colony-stimulating factor: partners in osteoclast biology,” Immunological Reviews, vol. 208, pp. 88–105, 2005. View at Publisher · View at Google Scholar
  14. T J Martin, “Paracrine regulation of osteoclast formation and activity: milestones in discovery,” Journal of Musculoskeletal Neuronal Interactions, vol. 4, no. 3, pp. 243–253, 2004. View at Google Scholar
  15. J Cao, L Venton, T Sakata, and B P Halloran, “Expression of RANKL and OPG correlates with age-related bone loss in male C57BL/6 mice,” Journal of Bone and Mineral Research, vol. 18, no. 2, pp. 270–277, 2003. View at Publisher · View at Google Scholar
  16. J J Cao, T J Wronski, U Iwaniec et al., “Aging increases stromal/osteoblastic cell-induced osteoclastogenesis and alters the osteoclast precursor pool in the mouse,” Journal of Bone and Mineral Research, vol. 20, no. 9, pp. 1659–1668, 2005. View at Publisher · View at Google Scholar
  17. A C Maurin, P M Chavassieux, L Frappart, P D Delmas, C M Serre, and P J Meunier, “Influence of mature adipocytes on osteoblast proliferation in human primary cocultures,” Bone, vol. 26, no. 5, pp. 485–489, 2000. View at Publisher · View at Google Scholar
  18. A C Maurin, P M Chavassieux, E Vericel, and P J Meunier, “Role of polyunsaturated fatty acids in the inhibitory effect of human adipocytes on osteoblastic proliferation,” Bone, vol. 31, no. 1, pp. 260–266, 2002. View at Publisher · View at Google Scholar
  19. E D Rosen and B M Spiegelman, “PPARγ: a nuclear regulator of metabolism, differentiation, and cell growth,” Journal of Biological Chemistry, vol. 276, no. 41, pp. 37731–37734, 2001. View at Publisher · View at Google Scholar
  20. Y Zhu, C Qi, J R Korenberg et al., “Structural organization of mouse peroxisome proliferator-activated receptor ? (mPPAR?) gene: alternative promoter use and different splicing yield two mPPAR? isoforms,” Proceedings of the National Academy of Sciences of the United States of America, vol. 92, no. 17, pp. 7921–7925, 1995. View at Publisher · View at Google Scholar
  21. L Fajas, D Auboeuf, E Raspé et al., “The organization, promoter analysis, and expression of the human PPAR? gene,” Journal of Biological Chemistry, vol. 272, no. 30, pp. 18779–18789, 1997. View at Publisher · View at Google Scholar
  22. L Fajas, J-C Fruchart, and J Auwerx, “PPARγ3 mRNA: a distinct PPARγ mRNA subtype transcribed from an independent promoter,” FEBS Letters, vol. 438, no. 1-2, pp. 55–60, 1998. View at Publisher · View at Google Scholar
  23. D Ren, T N Collingwood, E J Rebar, A P Wolffe, and H S Camp, “PPARγ knockdown by engineered transcription factors: exogenous PPARγ2 but not PPARγ1 reactivates adipogenesis,” Genes and Development, vol. 16, no. 1, pp. 27–32, 2002. View at Publisher · View at Google Scholar
  24. T M Willson, M H Lambert, and S A Kliewer, “Peroxisome proliferator-activated receptor γ and metabolic disease,” Annual Review of Biochemistry, vol. 70, pp. 341–367, 2001. View at Publisher · View at Google Scholar
  25. T Akune, S Ohba, S Kamekura et al., “PPAR? insufficiency enhances osteogenesis through osteoblast formation from bone marrow progenitors,” Journal of Clinical Investigation, vol. 113, no. 6, pp. 846–855, 2004. View at Publisher · View at Google Scholar
  26. T-A Cock, J Back, F Elefteriou et al., “Enhanced bone formation in lipodystrophic PPAR?(hyp/hyp) mice relocates haematopoiesis to the spleen,” EMBO Reports, vol. 5, no. 10, pp. 1007–1012, 2004. View at Publisher · View at Google Scholar
  27. S O Rzonca, L J Suva, D Gaddy, D C Montague, and B Lecka-Czernik, “Bone is a target for the antidiabetic compound rosiglitazone,” Endocrinology, vol. 145, no. 1, pp. 401–406, 2004. View at Publisher · View at Google Scholar
  28. V Sottile, K Seuwen, and M Kneissel, “Enhanced marrow adipogenesis and bone resorption in estrogen-deprived rats treated with the PPARgamma agonist BRL49653 (rosiglitazone),” Calcified Tissue International, vol. 75, no. 4, pp. 329–337, 2004. View at Publisher · View at Google Scholar
  29. M A Sorocéanu, D Miao, X-Y Bai, H Su, D Goltzman, and A C Karaplis, “Rosiglitazone impacts negatively on bone by promoting osteoblast/osteocyte apoptosis,” Journal of Endocrinology, vol. 183, no. 1, pp. 203–216, 2004. View at Publisher · View at Google Scholar
  30. A A Ali, R S Weinstein, S A Stewart, A M Parfitt, S C Manolagas, and R L Jilka, “Rosiglitazone causes bone loss in mice by suppressing osteoblast differentiation and bone formation,” Endocrinology, vol. 146, no. 3, pp. 1226–1235, 2005. View at Publisher · View at Google Scholar
  31. A C Bendixen, N K Shevde, K M Dienger, T M Willson, C D Funk, and J W Pike, “IL-4 inhibits osteoclast formation through a direct action on osteoclast precursors via peroxisome proliferator-activated receptor γ1,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 5, pp. 2443–2448, 2001. View at Publisher · View at Google Scholar
  32. R Okazaki, M Toriumi, S Fukumoto et al., “Thiazolidinediones inhibit osteoclast-like cell formation and bone resorption in vitro,” Endocrinology, vol. 140, no. 11, pp. 5060–5065, 1999. View at Publisher · View at Google Scholar
  33. A M Schwab, S Granholm, E Persson, B Wilkes, U H Lerner, and H H Conaway, “Stimulation of resorption in cultured mouse calvarial bones by thiazolidinediones,” Endocrinology, vol. 146, no. 10, pp. 4349–4361, 2005. View at Publisher · View at Google Scholar
  34. R Okazaki, M Miura, M Toriumi et al., “Short-term treatment with troglitazone decreases bone turnover in patients with type 2 diabetes mellitus,” Endocrine Journal, vol. 46, no. 6, pp. 795–801, 1999. View at Google Scholar
  35. A V Schwartz, D E Sellmeyer, E Vittinghoff et al., “Thiazolidinedione (TZD) use and bone loss in older diabetic adults,” Journal of Clinical Endocrinology & Metabolism. In press.
  36. S Ogawa, T Urano, T Hosoi et al., “Association of bone mineral density with a polymorphism of the peroxisome proliferator-activated receptor ? gene: PPAR? expression in osteoblasts,” Biochemical and Biophysical Research Communications, vol. 260, no. 1, pp. 122–126, 1999. View at Publisher · View at Google Scholar
  37. E-J Rhee, K-W Oh, W-Y Lee et al., “The effects of C161?T polymorphisms in exon 6 of peroxisome proliferator-activated receptor-? gene on bone mineral metabolism and serum osteoprotegerin levels in healthy middle-aged women,” American Journal of Obstetrics and Gynecology, vol. 192, no. 4, pp. 1087–1093, 2005. View at Publisher · View at Google Scholar
  38. A Meirhaeghe, L Fajas, F Gouilleux et al., “A functional polymorphism in a STAT5B site of the human PPAR?3 gene promoter affects height and lipid metabolism in a French population,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 23, no. 2, pp. 289–294, 2003. View at Publisher · View at Google Scholar
  39. D P Kiel, S Ferrari, L A Cupples et al., “Polymorphism in the PPAR? influence bone density in humans,” Journal of Bone and Mineral Research, vol. 20, p. S234, 2005. View at Google Scholar
  40. C Ackert-Bicknell and C J Rosen, “The genetics of PPARγ and the skeleton,” PPAR Research. In press.
  41. R F Klein, J Allard, Z Avnur et al., “Regulation of bone mass in mice by the lipoxygenase gene Alox15,” Science, vol. 303, no. 5655, pp. 229–232, 2004. View at Publisher · View at Google Scholar
  42. L F Bonewald, M Flynn, M Qiao, M R Dallas, G R Mundy, and B F Boyce, “Mice lacking 5-lipoxygenase have increased cortical bone thickness,” Advances in Experimental Medicine and Biology, vol. 433, pp. 299–302, 1997. View at Google Scholar
  43. T Urano, M Shiraki, M Fujita et al., “Association of a single nucleotide polymorphism in the lipoxygenase ALOX15 5'-flanking region (-5229G/A) with bone mineral density,” Journal of Bone and Mineral Metabolism, vol. 23, no. 3, pp. 226–230, 2005. View at Publisher · View at Google Scholar
  44. S Ichikawa, D L Koller, M L Johnson et al., “Human ALOX12, but not ALOX15, is associated with BMD in white men and women,” Journal of Bone and Mineral Research, vol. 21, no. 4, pp. 556–564, 2006. View at Publisher · View at Google Scholar
  45. C J Rosen, “Insulin-like growth factor I and bone mineral density: experience from animal models and human observational studies,” Best Practice and Research in Clinical Endocrinology and Metabolism, vol. 18, no. 3, pp. 423–435, 2004. View at Publisher · View at Google Scholar
  46. C J Rosen, “Insulin-like growth factor I and calcium balance: evolving concepts of an evolutionary process,” Endocrinology, vol. 144, no. 11, pp. 4679–4681, 2003. View at Publisher · View at Google Scholar
  47. A A Toogood, “Growth hormone (GH) status and body composition in normal ageing and in elderly adults with GH deficiency,” Hormone Research, vol. 60, no. suppl 1, pp. 105–111, 2003. View at Publisher · View at Google Scholar
  48. T L Clemens and S D Chernausek, “Genetic strategies for elucidating insulin-like growth factor action in bone,” Growth Hormone and IGF Research, vol. 14, no. 3, pp. 195–199, 2004. View at Publisher · View at Google Scholar
  49. C J Rosen, C L Ackert-Bicknell, M L Adamo et al., “Congenic mice with low serum IGF-I have increased body fat, reduced bone mineral density, and an altered osteoblast differentiation program,” Bone, vol. 35, no. 5, pp. 1046–1058, 2004. View at Publisher · View at Google Scholar
  50. B Lecka-Czernik, C Ackert-Bicknell, V Marmolejos et al., “Activation of peroxisome proliferator-activated receptor gamma (PPAR-?) by rosiglitazone suppresses components of the IGF regulatory system in vitro and in vivo,” Endocrinology. In press.
  51. S G Moore and K L Dawson, “Red and yellow marrow in the femur: age-related changes in appearance at MR imaging,” Radiology, vol. 175, no. 1, pp. 219–223, 1990. View at Google Scholar
  52. M W Hamrick, “Leptin, bone mass, and the thrifty phenotype,” Journal of Bone and Mineral Research, vol. 19, no. 10, pp. 1607–1611, 2004. View at Publisher · View at Google Scholar
  53. S Takeda, F Elefteriou, R Levasseur et al., “Leptin regulates bone formation via the sympathetic nervous system,” Cell, vol. 111, no. 3, pp. 305–317, 2002. View at Publisher · View at Google Scholar
  54. F Elefteriou, J D Ahn, S Takeda et al., “Leptin regulation of bone resorption by the sympathetic nervous system and CART,” Nature, vol. 434, no. 7032, pp. 514–520, 2005. View at Publisher · View at Google Scholar
  55. A H Berg, T P Combs, and P E Scherer, “ACRP30/adiponectin: an adipokine regulating glucose and lipid metabolism,” Trends in Endocrinology and Metabolism, vol. 13, no. 2, pp. 84–89, 2002. View at Publisher · View at Google Scholar
  56. L Lenchik, T C Register, F-C Hsu et al., “Adiponectin as a novel determinant of bone mineral density and visceral fat,” Bone, vol. 33, no. 4, pp. 646–651, 2003. View at Publisher · View at Google Scholar
  57. T Yokota, C SR Meka, K L Medina et al., “Paracrine regulation of fat cell formation in bone marrow cultures via adiponectin and prostaglandins,” Journal of Clinical Investigation, vol. 109, no. 10, pp. 1303–1310, 2002. View at Publisher · View at Google Scholar
  58. H S Berner, S P Lyngstadaas, A Spahr et al., “Adiponectin and its receptors are expressed in bone-forming cells,” Bone, vol. 35, no. 4, pp. 842–849, 2004. View at Publisher · View at Google Scholar
  59. X-H Luo, L-J Guo, L-Q Yuan et al., “Adiponectin stimulates human osteoblasts proliferation and differentiation via the MAPK signaling pathway,” Experimental Cell Research, vol. 309, no. 1, pp. 99–109, 2005. View at Publisher · View at Google Scholar
  60. Y Shinoda, M Yamaguchi, N Ogata et al., “Regulation of bone formation by adiponectin through autocrine/paracrine and endocrine pathways,” Journal of Cellular Biochemistry, vol. 99, no. 1, pp. 196–208, 2006. View at Publisher · View at Google Scholar
  61. P C Rambaut and A W Goode, “Skeletal changes during space flight,” Lancet, vol. 2, no. 8463, pp. 1050–1052, 1985. View at Publisher · View at Google Scholar
  62. P Minaire, C Edouard, M Arlot, and P J Meunier, “Marrow changes in paraplegic patients,” Calcified Tissue International, vol. 36, no. 3, pp. 338–340, 1984. View at Publisher · View at Google Scholar
  63. H Drissi, A Lomri, F Lasmoles, X Holy, E Zerath, and P J Marie, “Skeletal unloading induces biphasic changes in insulin-like growth factor-I mRNA levels and osteoblast activity,” Experimental Cell Research, vol. 251, no. 2, pp. 275–284, 1999. View at Publisher · View at Google Scholar
  64. L J Suva, D Gaddy, D S Perrien, R L Thomas, and D M Findlay, “Regulation of bone mass by mechanical loading: microarchitecture and genetics,” Current Osteoporosis Reports, vol. 3, no. 2, pp. 46–51, 2005. View at Publisher · View at Google Scholar
  65. S Ahdjoudj, F Lasmoles, X Holy, E Zerath, and P J Marie, “Transforming growth factor β2 inhibits adipocyte differentiation induced by skeletal unloading in rat bone marrow stroma,” Journal of Bone and Mineral Research, vol. 17, no. 4, pp. 668–677, 2002. View at Publisher · View at Google Scholar
  66. P J Marie and K Kaabeche, “PPAR gamma and control of bone mass in skeletal unloading,” PPAR Research. In press.
  67. M Seip and O Trygstad, “Generalized lipodystrophy, congenital and acquired (lipoatrophy),” Acta Paediatrica. Supplement, vol. 85, no. 413, pp. 2–28, 1996. View at Google Scholar
  68. J Westvik, “Radiological features in generalized lipodystrophy,” Acta Paediatrica. Supplement, vol. 413, pp. 44–51, 1996. View at Google Scholar
  69. T Takeda, M Hosokawa, S Takeshita et al., “A new murine model of accelerated senescence,” Mechanisms of Ageing and Development, vol. 17, no. 2, pp. 183–194, 1981. View at Publisher · View at Google Scholar
  70. R L Jilka, R S Weinstein, K Takahashi, A M Parfitt, and S C Manolagas, “Linkage of decreased bone mass with impaired osteoblastogenesis in a murine model of accelerated senescence,” Journal of Clinical Investigation, vol. 97, no. 7, pp. 1732–1740, 1996. View at Google Scholar
  71. O Kajkenova, B Lecka-Czernik, I Gubrij et al., “Increased adipogenesis and myelopoiesis in the bone marrow of SAMP6, a murine model of defective osteoblastogenesis and low turnover osteopenia,” Journal of Bone and Mineral Research, vol. 12, no. 11, pp. 1772–1779, 1997. View at Publisher · View at Google Scholar
  72. M J Silva, M D Brodt, M Ko, and Y Abu-Amer, “Impaired marrow osteogenesis is associated with reduced endocortical bone formation but does not impair periosteal bone formation in long bones of SAMP6 mice,” Journal of Bone and Mineral Research, vol. 20, no. 3, pp. 419–427, 2005. View at Publisher · View at Google Scholar
  73. K Takada, M Inaba, N Ichioka et al., “Treatment of senile osteoporosis in SAMP6 mice by intra-bone marrow injection of allogeneic bone marrow cells,” Stem Cells, vol. 24, no. 2, pp. 399–405, 2006. View at Publisher · View at Google Scholar
  74. J-H Hong and M B Yaffe, “TAZ: a β-catenin-like molecule that regulates mesenchymal stem cell differentiation,” Cell Cycle, vol. 5, no. 2, pp. 176–179, 2006. View at Google Scholar
  75. C B Cui, L F Cooper, X Yang, G Karsenty, and I Aukhill, “Transcriptional coactivation of bone-specific transcription factor Cbfa1 by TAZ,” Molecular and Cellular Biology, vol. 23, no. 3, pp. 1004–1013, 2003. View at Publisher · View at Google Scholar
  76. J-H Hong, E S Hwang, M T McManus et al., “TAZ, a transcriptional modulator of mesenchymal stem cell differentiation,” Science, vol. 309, no. 5737, pp. 1074–1078, 2005. View at Publisher · View at Google Scholar
  77. S K Zaidi, A J Sullivan, R Medina et al., “Tyrosine phosphorylation controls Runx2-mediated subnuclear targeting of YAP to repress transcription,” The EMBO Journal, vol. 23, no. 4, pp. 790–799, 2004. View at Publisher · View at Google Scholar
  78. M L Johnson, K Harnish, R Nusse, and W Van Hul, “LRP5 and Wnt signaling: a union made for bone,” Journal of Bone and Mineral Research, vol. 19, no. 11, pp. 1749–1757, 2004. View at Publisher · View at Google Scholar
  79. J J Westendorf, R A Kahler, and T M Schroeder, “Wnt signaling in osteoblasts and bone diseases,” Gene, vol. 341, no. 1-2, pp. 19–39, 2004. View at Publisher · View at Google Scholar
  80. Y Gong, R B Slee, N Fukai et al., “LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development,” Cell, vol. 107, no. 4, pp. 513–523, 2001. View at Publisher · View at Google Scholar
  81. L M Boyden, J Mao, J Belsky et al., “High bone density due to a mutation in LDL-receptor-related protein 5,” New England Journal of Medicine, vol. 346, no. 20, pp. 1513–1521, 2002. View at Publisher · View at Google Scholar
  82. P Babij, W Zhao, C Small et al., “High bone mass in mice expressing a mutant LRP5 gene,” Journal of Bone and Mineral Research, vol. 18, no. 6, pp. 960–974, 2003. View at Publisher · View at Google Scholar
  83. C N Bennett, S E Ross, K A Longo et al., “Regulation of Wnt signaling during adipogenesis,” Journal of Biological Chemistry, vol. 277, no. 34, pp. 30998–31004, 2002. View at Publisher · View at Google Scholar
  84. C N Bennett, K A Longo, W S Wright et al., “Regulation of osteoblastogenesis and bone mass by Wnt10b,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 9, pp. 3324–3329, 2005. View at Publisher · View at Google Scholar
  85. S L Holmen, C R Zylstra, A Mukherjee et al., “Essential role of ß-catenin in postnatal bone acquisition,” Journal of Biological Chemistry, vol. 280, no. 22, pp. 21162–21168, 2005. View at Publisher · View at Google Scholar
  86. D A II Glass, P Bialek, J D Ahn et al., “Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation,” Developmental Cell, vol. 8, no. 5, pp. 751–764, 2005. View at Publisher · View at Google Scholar
  87. L Tornvig, L Mosekilde, J Justesen, E Falk, and M Kassem, “Troglitazone treatment increases bone marrow adipose tissue volume but does not affect trabecular bone volume in mice,” Calcified Tissue International, vol. 69, no. 1, pp. 46–50, 2001. View at Publisher · View at Google Scholar
  88. J Justesen, L Mosekilde, M Holmes et al., “Mice deficient in 11ß-hydroxysteroid denydrogenase type 1 lack bone marrow adipocytes, but maintain normal bone formation,” Endocrinology, vol. 145, no. 4, pp. 1916–1925, 2004. View at Publisher · View at Google Scholar
  89. M Kveiborg, G Sabatakos, R Chiusaroli et al., “?FosB Induces osteosclerosis and decreases adipogenesis by two independent cell-autonomous mechanisms,” Molecular and Cellular Biology, vol. 24, no. 7, pp. 2820–2830, 2004. View at Publisher · View at Google Scholar
  90. M C Horowitz, AL M Bothwell, D G Hesslein, D L Pflugh, and D G Schatz, “B cells osteoblast and osteoclast development,” Immunological Reviews, vol. 208, pp. 141–153, 2005. View at Publisher · View at Google Scholar
  91. M J Reginato, S T Bailey, S L Krakow et al., “A potent antidiabetic thiazolidinedione with unique peroxisome proliferator-activated receptor ?-activating properties,” Journal of Biological Chemistry, vol. 273, no. 49, pp. 32679–32684, 1998. View at Publisher · View at Google Scholar