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Current Osteoporosis Reports

, Volume 12, Issue 2, pp 235–242 | Cite as

Fat and Bone Interactions

  • Sandra Bermeo
  • Krishanthi Gunaratnam
  • Gustavo DuqueEmail author
Hot Topic

Abstract

Fat and bone have a complicated relationship. Although obesity has been associated with low fracture risk, there is increasing evidence that some of the factors that are released by peripheral fat into the circulation may also have a deleterious effect on bone mass, thus, predisposing to fractures. More importantly, the local interaction between fat and bone within the bone marrow seems to play a significant role in the pathogenesis of age-related bone loss and osteoporosis. This “local interaction” occurs inside the bone marrow and is associated with the autocrine and paracrine release of fatty acids and adipokines, which affect the cells in their vicinity including the osteoblasts, reducing their function and survival. In this review, we explore the particularities of the fat and bone cell interactions within the bone marrow, their significance in the pathogenesis of osteoporosis, and the potential therapeutic applications that regulating marrow fat may have in the near future as a novel pharmacologic treatment for osteoporosis.

Keywords

Osteoporosis Fat Bone Adipocytes Osteoblasts Osteoclasts Osteocytes Mesenchymal stem cells Lamin A Aging Fractures Osteoporosis RUNX2 PPARγ BMP SMADs β-catenin 

Notes

Acknowledgement

The authors’ research cited in this review has been funded by project grants from the National Health and Medical Research Council (NHMRC) of Australia (Grants 632766 and 632767) and the Nepean Medical Research Foundation. The authors would like to thank PR Ebeling of the University of Melbourne and EF Eriksen of Oslo University Hospital for their review of the manuscript.

Compliance with Ethics Guidelines

Conflict of Interest

S. Bermeo declares no conflicts of interest.

K. Gunaratnam declares no conflicts of interest.

G. Duque declares no conflicts of interest.

Human and Animal Rights and Informed Consent

All studies by the authors involving animal subjects were performed after approval by the appropriate institutional review boards.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance ••Of major importance

  1. 1.
    Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Report of a WHO Study Group. World Health Organ Tech Rep Ser. 1994;843:1–129.Google Scholar
  2. 2.
    Manolagas SC. Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocr Rev. 2000;21:115–37.PubMedGoogle Scholar
  3. 3.
    Riggs BL, Khosla S, Melton III LJ. Sex steroids and the construction and conservation of the adult skeleton. Endocr Rev. 2002;23:279–302.PubMedCrossRefGoogle Scholar
  4. 4.
    Duque G, Troen BR. Understanding the mechanisms of senile osteoporosis: new facts for a major geriatric syndrome. J Am Geriatr Soc. 2008;56:935–41.PubMedCrossRefGoogle Scholar
  5. 5.
    Gunaratnam K, Vidal C, Gimble JM, et al. Mechanisms of palmitate-induced lipotoxicity in human osteoblasts. Endocrinology. 2014;155:108–16.PubMedCrossRefGoogle Scholar
  6. 6.
    Wauquier F, Philippe C, Leotoing L, et al. The free fatty acid receptor G protein-coupled receptor 40 (GPR40) protects from bone loss through inhibition of osteoclast differentiation. J Biol Chem. 2013;288:6542–51.PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Duque G. Bone and fat connection in aging bone. Curr Opin Rheumatol. 2008;20:429–34.PubMedCrossRefGoogle Scholar
  8. 8.•
    Ng A, Duque G. Osteoporosis as a Lipotoxic Disease. IBMS BoneKEy. 2010;7:108–23. Comprehensive review on the mechanisms of lipotoxicity in bone.CrossRefGoogle Scholar
  9. 9.
    Reid IR, Plank LD, Evans MC. Fat mass is an important determinant of whole body bone density in premenopausal women but not in men. J Clin Endocrinol Metab. 1992;75:779–82.PubMedGoogle Scholar
  10. 10.
    Albala C, Yanez M, Devoto E, et al. Obesity as a protective factor for postmenopausal osteoporosis. Int J Obes Relat Metab Disord. 1996;20:1027–32.PubMedGoogle Scholar
  11. 11.•
    Cohen A, Dempster DW, Recker RR, et al. Abdominal fat is associated with lower bone formation and inferior bone quality in healthy premenopausal women: a transiliac bone biopsy study. J Clin Endocrinol Metab. 2013;98:2562–72. Important study looking at the relationship between abdominal fat and bone mass.PubMedCrossRefGoogle Scholar
  12. 12.
    Bredella MA, Fazeli PK, Lecka-Czernik B, et al. IGFBP-2 is a negative predictor of cold-induced brown fat and bone mineral density in young non-obese women. Bone. 2013;53:336–9.PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Gilsanz V, Chalfant J, Mo AO, et al. Reciprocal relations of subcutaneous and visceral fat to bone structure and strength. J Clin Endocrinol Metab. 2009;94:3387–93.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.••
    Gimble JM, Nuttall ME. The relationship between adipose tissue and bone metabolism. Clin Biochem. 2012;45:874–9. Excellent review on the relationship between adipose tissue and bone.PubMedCrossRefGoogle Scholar
  15. 15.
    Boyle WJ, Simonet WS, Lacey DL. Osteoclast differentiation and activation. Nature. 2003;423:337–42.PubMedCrossRefGoogle Scholar
  16. 16.
    Di Iorgi N, Mo AO, Grimm K, et al. Bone acquisition in healthy young females is reciprocally related to marrow adiposity. J Clin Endocrinol Metab. 2010;95:2977–82.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Gimble JM, Robinson CE, Wu X, et al. The function of adipocytes in the bone marrow stroma: an update. Bone. 1996;19:421–8.PubMedCrossRefGoogle Scholar
  18. 18.•
    Kawai M, de Paula FJ, Rosen CJ. New insights into osteoporosis: the bone-fat connection. J Intern Med. 2012;272:317–29. General overview of the relationship between fat and bone focused on peripheral fat.PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Corre J, Planat-Benard V, Corberand JX, et al. Human bone marrow adipocytes support complete myeloid and lymphoid differentiation from human CD34 cells. Br J Haematol. 2004;127:344–7.PubMedCrossRefGoogle Scholar
  20. 20.•
    Mendez-Ferrer S, Michurina TV, Ferraro F, et al. Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. Nature. 2010;466:829–34. Excellent review on the mechanisms of mesenchymal stem cell differentiation.PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Si YL, Zhao YL, Hao HJ, et al. MSCs: biological characteristics, clinical applications and their outstanding concerns. Ageing Res Rev. 2011;10:93–103.PubMedCrossRefGoogle Scholar
  22. 22.
    Sethe S, Scutt A, Stolzing A. Aging of mesenchymal stem cells. Ageing Res Rev. 2006;5:91–116.PubMedCrossRefGoogle Scholar
  23. 23.
    Maurer MH. Proteomic definitions of mesenchymal stem cells. Stem Cells Int. 2011;2011:704256.PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    Dominici M, Le Blanc K, Mueller I, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006;8:315–7.PubMedCrossRefGoogle Scholar
  25. 25.••
    Boxall SA, Jones E. Markers for characterization of bone marrow multipotential stromal cells. Stem Cells Int. 2012;2012:975871. Comprehensive review on the mechanisms of stem cell differentiation.PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Casiraghi F, Perico N, Remuzzi G. Mesenchymal stromal cells to promote solid organ transplantation tolerance. Curr Opin Organ Transplant. 2013;18:51–8.PubMedCrossRefGoogle Scholar
  27. 27.
    Shah K. Mesenchymal stem cells engineered for cancer therapy. Adv Drug Deliv Rev. 2012;64:739–48.PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Ramakrishnan A, Torok-Storb B, Pillai MM. Primary marrow-derived stromal cells: isolation and manipulation. Methods Mol Biol. 2013;1035:75–101.PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.••
    Al-Nbaheen M, Vishnubalaji R, Ali D, et al. Human stromal (mesenchymal) stem cells from bone marrow, adipose tissue and skin exhibit differences in molecular phenotype and differentiation potential. Stem Cell Rev. 2013;9:32–43. Good review on the biology of mesenchymal stem cells.PubMedCentralPubMedCrossRefGoogle Scholar
  30. 30.
    Rastegar F, Shenaq D, Huang J, et al. Mesenchymal stem cells: molecular characteristics and clinical applications. World J Stem Cells. 2010;2:67–80.PubMedCentralPubMedCrossRefGoogle Scholar
  31. 31.
    Stolzing A, Jones E, McGonagle D, et al. Age-related changes in human bone marrow-derived mesenchymal stem cells: consequences for cell therapies. Mech Ageing Dev. 2008;129:163–73.PubMedCrossRefGoogle Scholar
  32. 32.
    Hammoudi TM, Rivet CA, Kemp ML, et al. Three-dimensional in vitro tri-culture platform to investigate effects of crosstalk between mesenchymal stem cells, osteoblasts, and adipocytes. Tissue Eng A. 2012;18:1686–97.CrossRefGoogle Scholar
  33. 33.
    Lu Z, Roohani-Esfahani S-I, Wang G, et al. Bone biomimetic microenvironment induces osteogenic differentiation of adipose tissue-derived mesenchymal stem cells. Nanomedicine. 2012;8:507–15.PubMedCrossRefGoogle Scholar
  34. 34.
    Elbaz A, Wu X, Rivas D, et al. Inhibition of fatty acid biosynthesis prevents adipocyte lipotoxicity on human osteoblasts in vitro. J Cell Mol Med. 2010;14:982–91.PubMedCrossRefGoogle Scholar
  35. 35.
    Rosen CJ, Ackert-Bicknell C, Rodriguez JP, et al. Marrow fat and the bone microenvironment: developmental, functional, and pathological implications. Crit Rev Eukaryot Gene Expr. 2009;19:109–24.PubMedCentralPubMedCrossRefGoogle Scholar
  36. 36.
    Kang S, Bennett CN, Gerin I, et al. Wnt signaling stimulates osteoblastogenesis of mesenchymal precursors by suppressing CCAAT/enhancer-binding protein alpha and peroxisome proliferator-activated receptor gamma. J Biol Chem. 2007;282:14515–24.PubMedCrossRefGoogle Scholar
  37. 37.
    Kurra S, Siris E. Diabetes and bone health: the relationship between diabetes and osteoporosis-associated fractures. Diabetes Metab Res Rev. 2011;27:430–5.PubMedCrossRefGoogle Scholar
  38. 38.
    Taxel P, Kaneko H, Lee SK, et al. Estradiol rapidly inhibits osteoclastogenesis and RANKL expression in bone marrow cultures in postmenopausal women: a pilot study. Osteoporos Int. 2008;19:193–9.PubMedCrossRefGoogle Scholar
  39. 39.
    Lau RY, Guo X. A review on current osteoporosis research: with special focus on disuse bone loss. J Osteoporos. 2011;2011:293808.PubMedCentralPubMedCrossRefGoogle Scholar
  40. 40.
    Hayashi K, Yamaguchi T, Yano S, et al. BMP/Wnt antagonists are upregulated by dexamethasone in osteoblasts and reversed by alendronate and PTH: potential therapeutic targets for glucocorticoid-induced osteoporosis. Biochem Biophys Res Commun. 2009;379:261–6.PubMedCrossRefGoogle Scholar
  41. 41.
    Gaur T, Lengner CJ, Hovhannisyan H, et al. Canonical WNT signaling promotes osteogenesis by directly stimulating Runx2 gene expression. J Biol Chem. 2005;280:33132–40.PubMedCrossRefGoogle Scholar
  42. 42.
    Rosen ED, MacDougald OA. Adipocyte differentiation from the inside out. Nat Rev Mol Cell Biol. 2006;7:885–96.PubMedCrossRefGoogle Scholar
  43. 43.•
    Takada I, Kouzmenko AP, Kato S. Wnt and PPAR gamma signaling in osteoblastogenesis and adipogenesis. Nat Rev Rheumatol. 2009;5:442–7. Excellent review on the role of Wnt and PPAR gamma in osteoblast and adipocyte differentiation.PubMedCrossRefGoogle Scholar
  44. 44.
    Komori T. Signaling networks in RUNX2-dependent bone development. J Cell Biochem. 2011;112:750–5.PubMedCrossRefGoogle Scholar
  45. 45.
    Yavropoulou MP, Yovos JG. The role of the Wnt signaling pathway in osteoblast commitment and differentiation. Hormones. 2007;6:279–94.PubMedCrossRefGoogle Scholar
  46. 46.
    Johnson ML, Rajamannan N. Diseases of Wnt signaling. Rev Endocr Metab Disord. 2006;7:41–9.PubMedCentralPubMedCrossRefGoogle Scholar
  47. 47.
    Johnson ML. LRP5 and bone mass regulation: where are we now? BoneKEy Rep. 2012;1:1.PubMedCentralPubMedCrossRefGoogle Scholar
  48. 48.
    Chang MK, Kramer I, Keller H, et al. Reversing LRP5-dependent osteoporosis and SOST deficiency-induced sclerosing bone disorders by altering Wnt signaling activity. J Bone Miner Res. 2014;29:29–42.PubMedCrossRefGoogle Scholar
  49. 49.
    Frost M, Andersen T, Gossiel F, et al. Levels of serotonin, sclerostin, bone turnover markers as well as bone density and microarchitecture in patients with high-bone-mass phenotype due to a mutation in Lrp5. J Bone Miner Res. 2011;26:1721–8.PubMedCrossRefGoogle Scholar
  50. 50.•
    Cawthorn WP, Bree AJ, Yao Y, et al. Wnt6, Wnt10a and Wnt10b inhibit adipogenesis and stimulate osteoblastogenesis through a beta-catenin-dependent mechanism. Bone. 2012;50:477–89. Relevant information on the role of Wnts in osteoblastogenesis.PubMedCentralPubMedCrossRefGoogle Scholar
  51. 51.
    Cristancho AG, Lazar MA. Forming functional fat: a growing understanding of adipocyte differentiation. Nat Rev Mol Cell Biol. 2011;12:722–34.PubMedCrossRefGoogle Scholar
  52. 52.
    Lin C, Jiang X, Dai Z, et al. Sclerostin mediates bone response to mechanical unloading through antagonizing Wnt/beta-catenin signaling. J Bone Miner Res. 2009;24:1651–61.PubMedCrossRefGoogle Scholar
  53. 53.•
    Duque G, Li W, Yeo LS, et al. Attenuated anabolic response to exercise in lamin A/C haploinsufficient mice. Bone. 2011;49:412–8. Initial report on the role of the proteins of the nuclear envelope in osteoblastogenesis.PubMedCrossRefGoogle Scholar
  54. 54.
    Piemonte S, Romagnoli E, Bratengeier C, et al. Serum sclerostin levels decline in post-menopausal women with osteoporosis following treatment with intermittent parathyroid hormone. J Endocrinol Invest. 2012;35:866–8.PubMedGoogle Scholar
  55. 55.
    Korvala J, Löija M, Mäkitie O, et al. Rare variations in WNT3A and DKK1 may predispose carriers to primary osteoporosis. Eur J Med Genet. 2012;55:515–9.PubMedCrossRefGoogle Scholar
  56. 56.
    Morvan F, Boulukos K, Clement-Lacroix P, et al. Deletion of a single allele of the Dkk1 gene leads to an increase in bone formation and bone mass. J Bone Miner Res. 2006;21:934–45.PubMedCrossRefGoogle Scholar
  57. 57.
    Padhi D, Jang G, Stouch B, et al. Single-dose, placebo-controlled, randomized study of AMG 785, a sclerostin monoclonal antibody. J Bone Miner Res. 2011;26:19–26.PubMedCrossRefGoogle Scholar
  58. 58.
    Glantschnig H, Hampton RA, Lu P, et al. Generation and selection of novel fully human monoclonal antibodies that neutralize Dickkopf-1 (DKK1) inhibitory function in vitro and increase bone mass in vivo. J Biol Chem. 2010;285:40135–47.PubMedCentralPubMedCrossRefGoogle Scholar
  59. 59.••
    Canalis E. Wnt signalling in osteoporosis: mechanisms and novel therapeutic approaches. Nat Rev Endocrinol. 2013;9:575–83. Excellent overview of the role of Wnt signaling in osteoporosis.PubMedCrossRefGoogle Scholar
  60. 60.
    Ling L, Nurcombe V, Cool SM. Wnt signaling controls the fate of mesenchymal stem cells. Gene. 2009;433:1–7.PubMedCrossRefGoogle Scholar
  61. 61.••
    Chen G, Deng C, Li YP. TGF-beta and BMP signaling in osteoblast differentiation and bone formation. Int J Biol Sci. 2012;8:272–88. Comprehensive assessment of the role of BMPs in bone formation.PubMedCentralPubMedCrossRefGoogle Scholar
  62. 62.
    Piek E, Sleumer LS, van Someren EP, et al. Osteo-transcriptomics of human mesenchymal stem cells: accelerated gene expression and osteoblast differentiation induced by vitamin D reveals c-MYC as an enhancer of BMP2-induced osteogenesis. Bone. 2010;46:613–27.PubMedCrossRefGoogle Scholar
  63. 63.•
    Duque G, Li W, Vidal C, et al. Pharmacological inhibition of PPARgamma increases osteoblastogenesis and bone mass in male C57BL/6 mice. J Bone Miner Res. 2013;28:639–48. Most recent report on the therapeutic applications of PPAR gamma inhibition in osteoporosis.PubMedCrossRefGoogle Scholar
  64. 64.
    Swift J, Ivanovska IL, Buxboim A, et al. Nuclear lamin-A scales with tissue stiffness and enhances matrix-directed differentiation. Science. 2013;341:1240104.PubMedCrossRefGoogle Scholar
  65. 65.
    Crisp M, Burke B. The nuclear envelope as an integrator of nuclear and cytoplasmic architecture. FEBS Lett. 2008;582:2023–32.PubMedCrossRefGoogle Scholar
  66. 66.
    Andres V, Gonzalez JM. Role of A-type lamins in signaling, transcription, and chromatin organization. J Cell Biol. 2009;187:945–57.PubMedCentralPubMedCrossRefGoogle Scholar
  67. 67.
    Akter R, Rivas D, Geneau G, et al. Effect of lamin A/C knockdown on osteoblast differentiation and function. J Bone Miner Res. 2009;24:283–93.PubMedCrossRefGoogle Scholar
  68. 68.
    Rauner M, Sipos W, Goettsch C, et al. Inhibition of lamin A/C attenuates osteoblast differentiation and enhances RANKL-dependent osteoclastogenesis. J Bone Miner Res. 2009;24:78–86.PubMedCrossRefGoogle Scholar
  69. 69.
    Duque G, Rivas D. Age-related changes in lamin A/C expression in the osteoarticular system: laminopathies as a potential new aging mechanism. Mech Ageing Dev. 2006;127:378–83.PubMedCrossRefGoogle Scholar
  70. 70.
    Rivas D, Li W, Akter R, et al. Accelerated features of age-related bone loss in zmpste24 metalloproteinase-deficient mice. J Gerontol A Biol Sci Med Sci. 2009;64:1015–24.PubMedCrossRefGoogle Scholar
  71. 71.
    Wu X, Tu X, Joeng KS, et al. Rac1 activation controls nuclear localization of beta-catenin during canonical Wnt signaling. Cell. 2008;133:340–53.PubMedCentralPubMedCrossRefGoogle Scholar
  72. 72.
    Kumeta M, Yoshimura SH, Hejna J, et al. Nucleocytoplasmic shuttling of cytoskeletal proteins: molecular mechanism and biological significance. Int J Cell Biol. 2012;2012:494902.PubMedCentralPubMedCrossRefGoogle Scholar
  73. 73.
    Tilgner K, Wojciechowicz K, Jahoda C, et al. Dynamic complexes of A-type lamins and emerin influence adipogenic capacity of the cell via nucleocytoplasmic distribution of beta-catenin. J Cell Sci. 2009;122:401–13.PubMedCentralPubMedCrossRefGoogle Scholar
  74. 74.
    Wan Y. PPARγ in bone homeostasis. Trends Endocrinol Metab. 2010;21:722–8.PubMedCrossRefGoogle Scholar
  75. 75.
    Vidal C, Bermeo S, Li W, et al. Interferon gamma inhibits adipogenesis in vitro and prevents marrow fat infiltration in oophorectomized mice. Stem Cells. 2012;30:1042–8.PubMedCrossRefGoogle Scholar
  76. 76.
    Fournier C, Perrier A, Thomas M, et al. Reduction by strontium of the bone marrow adiposity in mice and repression of the adipogenic commitment of multipotent C3H10T1/2 cells. Bone. 2012;50:499–509.PubMedCrossRefGoogle Scholar
  77. 77.•
    Driessler F, Baldock PA. Hypothalamic regulation of bone. J Mol Endocrinol. 2010;45:175–81. Original evidence on hypothalamic regulation of bone.PubMedCrossRefGoogle Scholar
  78. 78.
    Yadav VK, Oury F, Tanaka KF, et al. Leptin-dependent serotonin control of appetite: temporal specificity, transcriptional regulation, and therapeutic implications. J Exp Med. 2011;208:41–52.PubMedCentralPubMedCrossRefGoogle Scholar
  79. 79.
    Mason JJ, Williams BO. SOST and DKK: antagonists of LRP family signaling as targets for treating bone disease. J Osteoporos. 2010;2010:460120.Google Scholar
  80. 80.
    Inose H, Zhou B, Yadav VK, et al. Efficacy of serotonin inhibition in mouse models of bone loss. J Bone Miner Res. 2011;26:2002–11.PubMedCrossRefGoogle Scholar
  81. 81.
    Confavreux CB. Bone: from a reservoir of minerals to a regulator of energy metabolism. Kidney Int. 2011;79 Suppl 121:S14–9.CrossRefGoogle Scholar
  82. 82.
    Chen X, Tian HM, Yu XJ. Bone delivers its energy information to fat and islets through osteocalcin. Orthop Surg. 2012;4:114–7.PubMedCrossRefGoogle Scholar
  83. 83.
    Fazeli PK, Horowitz MC, MacDougald OA, et al. Marrow fat and bone–new perspectives. J Clin Endocrinol Metab. 2013;98:935–45.PubMedCentralPubMedCrossRefGoogle Scholar
  84. 84.•
    Verma S, Rajaratnam JH, Denton J, et al. Adipocytic proportion of bone marrow is inversely related to bone formation in osteoporosis. J Clin Pathol. 2002;55:693–8. Original paper demonstrating the inverse relationship between marrow fat and bone mass in humans.PubMedCentralPubMedCrossRefGoogle Scholar
  85. 85.
    Jilka RL, Weinstein RS, Parfitt AM, et al. Quantifying osteoblast and osteocyte apoptosis: challenges and rewards. J Bone Miner Res. 2007;22:1492–501.PubMedCrossRefGoogle Scholar
  86. 86.
    Meunier P, Aaron J, Edouard C, et al. Osteoporosis and the replacement of cell populations of the marrow by adipose tissue. A quantitative study of 84 iliac bone biopsies. Clin Orthop Relat Res. 1971;80:147–54.PubMedCrossRefGoogle Scholar
  87. 87.
    Wehrli FW, Hopkins JA, Hwang SN, et al. Cross-sectional study of osteopenia with quantitative MR imaging and bone densitometry. Radiology. 2000;217:527–38.PubMedCrossRefGoogle Scholar
  88. 88.
    Kim JE, Ahn MW, Baek SH, et al. AMPK activator, AICAR, inhibits palmitate-induced apoptosis in osteoblast. Bone. 2008;43:394–404.PubMedCrossRefGoogle Scholar
  89. 89.
    Maurin AC, Chavassieux PM, Frappart L, et al. Influence of mature adipocytes on osteoblast proliferation in human primary co-cultures. Bone. 2000;26:485–9.PubMedCrossRefGoogle Scholar
  90. 90.
    Gasparrini M, Rivas D, Elbaz A, et al. Differential expression of cytokines in subcutaneous and marrow fat of aging C57BL/6 J mice. Exp Gerontol. 2009;44:613–8.PubMedCrossRefGoogle Scholar
  91. 91.
    Reya T, Clevers H. Wnt signaling in stem cells and cancer. Nature. 2005;434:843–50.PubMedCrossRefGoogle Scholar
  92. 92.
    Moon RT, Kohn AD, De Ferrari GV, et al. WNT and beta-catenin signaling: diseases and therapies. Nat Rev Genet. 2004;5:691–701.PubMedCrossRefGoogle Scholar
  93. 93.
    Tong J, Li W, Vidal C, et al. Lamin A/C deficiency is associated with fat infiltration of muscle and bone. Mech Ageing Dev. 2011;132:552–9.PubMedCrossRefGoogle Scholar
  94. 94.
    Shearer BG, Billin AN. The next generation of PPAR drugs: do we have the tools to find them? Biochim Biophys Acta. 2007;1771:1082–93.PubMedCrossRefGoogle Scholar
  95. 95.
    Goto T, Kim Y-I, Takahashi N, et al. Natural compounds regulate energy metabolism by the modulating the activity of lipid-sensing nuclear receptors. Mol Nutr Food Res. 2013;57:20–33.PubMedCrossRefGoogle Scholar
  96. 96.
    Duque G, Huang DC, Macoritto M, et al. Autocrine regulation of interferon gamma in mesenchymal stem cells plays a role in early osteoblastogenesis. Stem Cells. 2009;27:550–8.PubMedCrossRefGoogle Scholar
  97. 97.
    Duque G, Huang DC, Dion N, et al. Interferon-gamma plays a role in bone formation in vivo and rescues osteoporosis in ovariectomized mice. J Bone Miner Res. 2011;26:1472–83.PubMedCrossRefGoogle Scholar
  98. 98.
    Schmid B, Rippmann JF, Tadayyon M, et al. Inhibition of fatty acid synthase prevents preadipocyte differentiation. Biochem Biophys Res Commun. 2005;328:1073–82.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Sandra Bermeo
    • 1
  • Krishanthi Gunaratnam
    • 1
  • Gustavo Duque
    • 1
    Email author
  1. 1.Ageing Bone Research Program, Sydney Medical School NepeanThe University of SydneyPenrithAustralia

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