UCSF DIABETES, ENDOCRINOLOGY & METABOLISM TRAINING PROGRAM FACULTY RESEARCH SUMMARIES
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HALLORAN, BERNARD, Ph.D. Department of Medicine and Physiology
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My primary research interest is in mammalian cell senescence and human aging with a focus on bone and age-related osteoporosis. We study the aging process in mouse and human bone cells and how aging affects bone cell function. It is thought that the loss of bone with aging is a consequence, in part, of functional and proliferative senescence of osteoblasts and osteoclast stem cell populations in the marrow. Bone marrow provides a source of osteoblast and osteoclast progenitors for the study of bone cell recruitment, maturation and function. We harvest marrow from animals and humans of different ages and selectively grow relatively pure populations of osteoblasts (OBs) and osteoclasts (OCs). As a function of donor age, the processes of osteoprogenitor recruitment and cell differentiation in vitro change. The phenotype of the bone cell gradually changes or “drifts” with advancing age of the donor. Coupling between bone formation and resorption is disrupted as a consequence of osteoblast up-regulation of RANKL expression and down-regulation of expression of the naturally opposing factor, osteoprotegerin (OPG). To correct this imbalance and reverse or prevent bone loss, clinical trials are now testing the efficacy of OPG administration. This should lead to the development of the most effective, most rational therapeutic agent for age-related bone loss to date.
Selected References
Sakata, T., Wang, Y., Halloran, B., ElAlieh, H., Cao, J., Bikle, D., Skeletal unloading induces resistance to IGF-I by inhibiting activation of the IGF-I signaling pathways. J. Bone Min. Res. 19(3):436-446, 2004.
Huang, J., Sakata, T., Pfleger, L., Bencsik, M., Halloran, B., Bikle, D., Nissenson, R., Effects of parathyroid hormone on RANKL and OPG expression during osteoblast differentiation. J. Bone Min. Res. 19(2):235-244, 2004.
Cao JJ, Wronski TJ, Iwaniec U, Phleger L, Kurimoto P, Boudignon B, Halloran BP. Aging increases stromal/osteoblastic cell-induced osteoclastogenesis and alters the osteoclast precursor pool in the mouse. J Bone Miner Res. 2005 Sep;20(9):1659-68.