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Skeletal remodeling in health and disease

Abstract

The use of genetically manipulated mouse models, gene and protein discovery and the cataloguing of genetic mutations have each allowed us to obtain new insights into skeletal morphogenesis and remodeling. These techniques have made it possible to identify molecules that are obligatory for specific cellular functions, and to exploit these molecules for therapeutic purposes. New insights into the pathophysiology of diseases have also enabled us to understand molecular defects in a way that was not possible a decade ago. This review summarizes our current understanding of the carefully orchestrated cross-talk between cells of the bone marrow and between bone cells and the brain through which bone is constantly remodeled during adult life. It also highlights molecular aberrations that cause bone cells to become dysfunctional, as well as therapeutic options and opportunities to counteract skeletal loss.

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Figure 1: Diverse functions and regulation of the osteoblast.
Figure 2: Molecular mechanisms underlying osteoclastogenesis and bone resorption.
Figure 3: Neural and neurohumoral regulation of bone mass.

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Acknowledgements

I thank J. Iqbal (Medical Scientist Training Program student) for developing the figures, M.J. Sweeney for editorial assistance and L. Sun, B.S. Moonga, E. Abe and H.C. Blair for helpful critiques. I acknowledge the support of the US National Institutes of Health (grants AG14907, DK70526 and AG23176) and Department of Veteran Affairs (Merit Award and Geriatrics Research Education and Clinical Center).

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Speaker and lecturer: Alliance for Better Health and Merck.

Ad hoc boards: Roche, GlaxoSmithKline, and Proctor & Gamble.

Research grants to Mount Sinai: Procter & Gamble, Genzyme, and Servier (IRIS, Paris).

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Zaidi, M. Skeletal remodeling in health and disease. Nat Med 13, 791–801 (2007). https://doi.org/10.1038/nm1593

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