, Volume 23, Issue 2–3, pp 183–188

Bone and fat

Old questions, new insights
Clinical Update


Until recently, adipose tissue was considered to serve only as a triglyceride reservoir and was relegated to a passive endocrine role. With the discovery of leptin and other adipokines, adipose tissue is now recognized as an active participant in systemic metabolism. This review focuses on the complex relationship existing between adipose tissue and bone metabolism and differentiation. It explores the paradigms that have shaped the past decade’s research and what these findings forecast for the future. Particular attention is given to the multipotent adult stem cell populations that reside within bone and fat. These adult stem cells have critical importance to the emerging field of tissue engineering and regenerative medicine.

Key Words

Adipocyte adult stem cell bone differentiation osteoblast stromal cell 


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  1. 1.
    Bornstein, S. R., Licinio, J., Tauchnitz, R., et al. (1998). J. Clin. Endocrinol. Metab. 83, 280–283.PubMedCrossRefGoogle Scholar
  2. 2.
    Gavrila, A., Peng, C. K., Chan, J. L., Mietus, J. E., Goldberger, A. L., and Mantzoros, C. S. (2003). J. Clin. Endocrinol. Metab. 88, 2838–2843.PubMedCrossRefGoogle Scholar
  3. 3.
    Patten, B. M. and Carlson, B. M. (eds.) (1974). Third Edition Foundations of Embryology. McGraw Hill: New York, NY.Google Scholar
  4. 4.
    Gimble, J. and Guilak, F. (2003). Curr. Top. Dev. Biol. 58, 137–160.PubMedGoogle Scholar
  5. 5.
    Tavassoli, M. and Crosby, W. H. (1970). Science 169, 291–293.PubMedCrossRefGoogle Scholar
  6. 5a.
    Tavassoli, M., Maniatis, A., and Crosby, W. H. (1974). Blood 43, 33–38.PubMedGoogle Scholar
  7. 6.
    Maniatis, A., Tavassoli, M., and Crosby, W. H. (1971). Blood 37, 581–586.PubMedGoogle Scholar
  8. 7.
    Bathija, A., Davis, S., and Trubowitz, S. (1978). Am. J. Hematol. 5, 315–321.PubMedCrossRefGoogle Scholar
  9. 8.
    Brookoff, D. and Weiss, L. (1982). Blood 60, 1337–1344.PubMedGoogle Scholar
  10. 8a.
    Tavassoli, M., Eastlund, D. T., Yam, L. T., Neiman, R. S., and Finkel, H. (1976). Scand. J. Haematol. 16, 311–319.PubMedCrossRefGoogle Scholar
  11. 9.
    Hussain, M. M., Mahley, R. W., Boyles, J. K., Fainaru, M., Brecht, W. J., and Lindquist, P. A. (1989). J. Biol. Chem. 264, 9571–9582.PubMedGoogle Scholar
  12. 10.
    Hussain, M. M., Mahley, R. W., Boyles, J. K., Lindquist, P. A., Brecht, W. J., and Innerarity, T. L. (1989). J. Biol. Chem. 264, 17931–17938.PubMedGoogle Scholar
  13. 11.
    Seaman, J. P., Kjeldsbert, C. R., and Linker, A. (1978). Hum. Pathol. 9, 685–692.PubMedCrossRefGoogle Scholar
  14. 12.
    Bathija, A., Davis, S., and Trubowitz, S. (1978). Am. J. Hematol. 6, 191–198.CrossRefGoogle Scholar
  15. 13.
    Custer, R. P. and Ahlfeldt, F. E. (1932). J. Lab. Clin. Med. 17, 960–962.Google Scholar
  16. 14.
    Hartsock, R. J., Smith, E. B., and Petty, C. S. (1965). Am. J. Clin. Pathol. 43, 326–331.PubMedGoogle Scholar
  17. 15.
    Babyn, P. S., Ranson, M., and McCarville, M. E. (1998). Magn. Reson. Imaging Clin. N. Am. 6, 473–495.PubMedGoogle Scholar
  18. 16.
    Huggins, C. and Blocksom, B. H. (1936). J. Exp. Med. 64, 253–274.CrossRefPubMedGoogle Scholar
  19. 17.
    Huggins, C. and Noonan, W. J. (1936). J. Exp. Med. 64, 275–280.CrossRefPubMedGoogle Scholar
  20. 18.
    Huggins, C., Blocksom, B. H., and Noonan, W. J. (1936). Am. J. Physiol. 115, 395–401.Google Scholar
  21. 19.
    Petrakis, N. L. (1966). Am. J. Phys. Anth. 25, 119–130.CrossRefGoogle Scholar
  22. 20.
    Weiss, L. P. and Wislocki, G. B. (1956). Anat. Rec. 126, 143–163.PubMedCrossRefGoogle Scholar
  23. 21.
    Meunier, P., Aaron, J., Edouard, C., and Vignon, G. (1971). Clin. Orthop. 80, 147–154.PubMedCrossRefGoogle Scholar
  24. 22.
    Justesen, J., Stenderup, K., Ebbesen, E. N., Mosekilde, L., Steiniche, T., and Kassem, M. (2001). Biogerontology 2, 165–171.PubMedCrossRefGoogle Scholar
  25. 23.
    Friedenstein, A. J. (1976). Int. Rev. Cytol. 47, 327–359.PubMedCrossRefGoogle Scholar
  26. 24.
    Grigoriadis, A. E., Heersche, J. N., and Aubin, J. E. (1988). J. Cell Biol. 106, 2139–2151.PubMedCrossRefGoogle Scholar
  27. 25.
    Nuttall, M. E., Patton, A. J., Olivera, D. L., Nadeau, D. P., and Gowen, M. (1998). J. Bone Miner. Res. 13, 371–382.PubMedCrossRefGoogle Scholar
  28. 26.
    Pittenger, M. F., Mackay, A. M., Beck, S. C., et al. (1999). Science 284, 143–147.PubMedCrossRefGoogle Scholar
  29. 27.
    D’Ippolito, G., Schiller, P. C., Ricordi, C., Roos, B. A., and Howard, G. A. (1999). J. Bone Miner. Res. 14, 1115–1122.PubMedCrossRefGoogle Scholar
  30. 28.
    Stenderup, K., Justesen, J., Eriksen, E. F., Rattan, S. I., and Kassem, M. (2001). J. Bone Miner. Res. 16, 1120–1129.PubMedCrossRefGoogle Scholar
  31. 29.
    Justesen, J., Stenderup, K., Eriksen, E. F., and Kassem, M. (2002). Calcif. Tissue Int. 71, 36–44.PubMedCrossRefGoogle Scholar
  32. 30.
    Beresford, J. N., Bennett, J. H., Devlin, C., Leboy, P. S., and Owen, M. E. (1992). J. Cell Sci. 102, 341–351.PubMedGoogle Scholar
  33. 31.
    Dorheim, M. A., Sullivan, M., Dandapani, V., et al. (1993). J. Cell Physiol. 154, 317–328.PubMedCrossRefGoogle Scholar
  34. 32.
    Lehmann, J. M., Moore, L. B., Smith-Oliver, T. A., Wilkison, W. O., Willson, T. M., and Kliewer, S. A. (1995). J. Biol. Chem. 270, 12953–12956.PubMedCrossRefGoogle Scholar
  35. 33.
    Gimble, J. M., Robinson, C. E., Wu, X., et al. (1996). Mol. Pharmacol. 50, 1087–1094.PubMedGoogle Scholar
  36. 34.
    Lecka-Czernik, B., Gubrij, I., Moerman, E. J., et al. (1999). J. Cell Biochem. 74, 357–371.PubMedCrossRefGoogle Scholar
  37. 35.
    Lecka-Czernik, B., Moerman, E. J., Grant, D. F., Lehmann, J. M., Manolagas, S. C., and Jilka, R. L. (2002). Endocrinology 143, 2376–2384.PubMedCrossRefGoogle Scholar
  38. 36.
    Tornvig, L., Mosekilde, L. I., Justesen, J., Falk, E., and Kassem, M. (2001). Calcif. Tissue Int. 69, 46–50.PubMedCrossRefGoogle Scholar
  39. 37.
    Rzonca, S. O., Suva, L. J., Gaddy, D., Montague, D. C., and Lecka-Czernik, B. (2004). Endocrinology 145, 401–406.PubMedCrossRefGoogle Scholar
  40. 38.
    Ross, S. E., Hemati, N., Longo, K. A., et al. (2000). Science 289, 950–953.PubMedCrossRefGoogle Scholar
  41. 38a.
    Bennett, C. N., Ross, S. E., Longo, K. A., et al. (2002). J. Biol. Chem. 277, 30998–31004.PubMedCrossRefGoogle Scholar
  42. 39.
    Gong, Y., Slee, R. B., Fukai, N., et al.; Osteoporosis-Pseudoglioma Syndrome Collaborative Group. (2001). Cell 107, 513–523.PubMedCrossRefGoogle Scholar
  43. 40.
    Boyden, L. M., Mao, J., Belsky, J., et al. (2002). N. Engl. J. Med. 346, 1513–1521.PubMedCrossRefGoogle Scholar
  44. 41.
    Little, R. D., Carulli, J. P., Del Mastro, R. G., et al. (2002). Am. J. Hum. Genet. 70, 11–19.PubMedCrossRefGoogle Scholar
  45. 42.
    Gimble, J. M., Morgan, C., Kelly, K., et al. (1995). J. Cell Biochem. 58, 393–402.PubMedCrossRefGoogle Scholar
  46. 43.
    Skillington, J., Choy, L., and Derynck, R. (2002). J. Cell Biol. 159, 135–146.PubMedCrossRefGoogle Scholar
  47. 44.
    Chen, D., Ji, X., Harris, M. A., et al. (1998). J. Cell Biol. 142, 295–305.PubMedCrossRefGoogle Scholar
  48. 45.
    Ji, X., Chen, D., Xu, C., Harris, S. E., Mundy, G. R., and Yoneda, T. (2000). J. Bone Miner. Metab. 18, 132–139.PubMedCrossRefGoogle Scholar
  49. 46.
    Thomas, T., Gori, F., Khosla, S., Jensen, M. D., Burguera, B., and Riggs, B. L. (1999). Endocrinology 140, 1630–1638.PubMedCrossRefGoogle Scholar
  50. 47.
    Roemmich, J. N., Clark, P. A., Mantzoros, C. S., Gurgol, C. M., Weltman, A., and Rogol, A. D. (2003). J. Clin. Endocrinol. Metab. 88, 599–604.PubMedCrossRefGoogle Scholar
  51. 48.
    Ducy, P., Amling, M., Takeda, S., et al. (2000). Cell 100, 197–207.PubMedCrossRefGoogle Scholar
  52. 49.
    Takeda, S., Elefteriou, F., Levasseur, R., et al. (2002). Cell 111, 305–317.PubMedCrossRefGoogle Scholar
  53. 50.
    Owen, M. (1988). J. Cell Sci. Suppl. 10, 63–76.PubMedGoogle Scholar
  54. 51.
    Caplan, A. I. (1994). Clin. Plast. Surg. 21, 429–435.PubMedGoogle Scholar
  55. 52.
    Gimble, J. M. (1990). The New Biologist 2, 304–312.PubMedGoogle Scholar
  56. 53.
    Gimble, J. M., Robinson, C. E., Wu, X., and Kelly, K. A. (1996). Bone 19, 421–428.PubMedCrossRefGoogle Scholar
  57. 54.
    Nuttall, M. E. and Gimble, J. M. (2000). Bone 27, 177–184.PubMedCrossRefGoogle Scholar
  58. 55.
    Bianco, P. and Robey, P. G. (2001). Nature 414, 118–121.PubMedCrossRefGoogle Scholar
  59. 56.
    Kaplan, F. S. and Shore, E. M. (2000). J. Bone Miner. Res. 15, 2084–2094.PubMedCrossRefGoogle Scholar
  60. 57.
    Shore, E. M., Ahn, J., Jan de Beur, S., et al. (2002). N. Engl. J. Med. 346, 99–106.PubMedCrossRefGoogle Scholar
  61. 58.
    Halvorsen, Y. D., Bond, A., Sen, A., et al. (2001). Metabolism 50, 407–413.PubMedCrossRefGoogle Scholar
  62. 59.
    Halvorsen, Y. D., Franklin, D., Bond, A. L., et al. (2001). Tissue Eng. 7, 729–741.PubMedCrossRefGoogle Scholar
  63. 60.
    Sen, A., Lea-Currie, Y. R., Sujkowski, D., et al. (2001). J. Cell. Biochem. 81, 312–319.PubMedCrossRefGoogle Scholar
  64. 61.
    Erickson, G. R., Gimble, J. M., Franklin, D. M., Rice, H. E., Awad, H., and Guilak, F. (2002). Biochem. Biophys. Res. Commun. 290, 763–769.PubMedCrossRefGoogle Scholar
  65. 62.
    Safford, K. M., Hicok, K. C., Safford, S. D., et al. (2002). Biochem. Biophys. Res. Commun. 294, 371–379.PubMedCrossRefGoogle Scholar
  66. 63.
    Wickham, M. Q., Erickson, G. R., Gimble, J. M., Vail, T. P., and Guilak, F. (2003). Clin. Orthop. 412, 196–212.PubMedCrossRefGoogle Scholar
  67. 64.
    Zuk, P. A., Zhu, M., Mizuno, H., et al. (2001). Tissue Eng. 7, 211–228.PubMedCrossRefGoogle Scholar
  68. 65.
    Zuk, P. A., Zhu, M., Ashjian, P., et al. (2002). Mol. Biol. Cell. 13, 4279–4295.PubMedCrossRefGoogle Scholar
  69. 66.
    Aust, L., Devlin, B. H., Foster, S. J., et al. (2004). Cytotherapy 6, 1–8.CrossRefGoogle Scholar
  70. 67.
    Gronthos, S., Franklin, D. M., Leddy, H. A., Storms, R., and Gimble, J. M. (2001). J. Cell Physiol. 189, 54–63.PubMedCrossRefGoogle Scholar
  71. 68.
    De Ugarte, D. A., Alfonso, Z., Zuk, P. A., et al. (2003). Immunol. Lett. 89, 267–270.PubMedCrossRefGoogle Scholar
  72. 69.
    Hicok, K. C., du Laney, T. V., Zhou, Y. S., et al. (2004). Tissue Engineering 10, 371–380.PubMedCrossRefGoogle Scholar
  73. 70.
    Justesen, J., Pedersen, S. B., Stenderup, K., and Kassem, M. (2004). Tissue Engineering, in press.Google Scholar
  74. 71.
    Safford, K. M., Safford, S. D., Gimble, J. M., Shetty, A. K., and Rice, H. E. (2004). Exp. Neurol., in press.Google Scholar
  75. 72.
    Ashjian, P. H., Elbarbary, A. S., Edmonds, B., et al. (2003). Plast. Reconstr. Surg. 111, 1922–1931.PubMedCrossRefGoogle Scholar
  76. 73.
    Mizuno, H., Zuk, P. A., Zhu, M., Lorenz, H. P., Benhaim, P., and Hedrick, M. H. (2002). Plast. Reconstr. Surg. 109, 199–209.PubMedCrossRefGoogle Scholar
  77. 74.
    Rangappa, S., Fen, C., Lee, E. H., Bongso, A., and Wei, E. S. (2003). Ann. Thorac. Surg. 75, 775–779.PubMedCrossRefGoogle Scholar
  78. 75.
    Garcia-Olmo, D., Garcia-Arranz, M., Garcia, L. G., et al. (2003). Int. J. Colorectal Dis. 18, 451–454.PubMedCrossRefGoogle Scholar
  79. 76.
    Guilak, F., Butler, D. L., and Goldstein, S. A. (2001). Clin. Orthop. 391(Suppl.), S295-S305.PubMedGoogle Scholar
  80. 77.
    Reaven, G. M. (2000). Curr. Atheroscler. Rep. 2, 503–507.PubMedCrossRefGoogle Scholar
  81. 78.
    Leibel, R. L. (2002). Nutr. Rev. 60, S15-S19.PubMedCrossRefGoogle Scholar
  82. 79.
    Ouchi, N., Kihara, S., Funahashi, T., Matsuzawa, Y., and Walsh, K. (2003). Curr. Opin. Lipidol. 14, 561–566.PubMedCrossRefGoogle Scholar
  83. 80.
    Hotamisligil, G. S. (1999). Expl. Clin. Endocrinol. Diabetes 107, 119–125.CrossRefGoogle Scholar
  84. 81.
    Yokota, T., Meka, C. S., Medina, K. L., et al. (2002). J. Clin. Invest. 109, 1303–1310.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2004

Authors and Affiliations

  1. 1.Stem Cell Laboratory, Pennington Biomedical Research CenterLouisiana State UniversityBaton Rouge
  2. 2.CentocorMalvern

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