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RANKL/OPG; Critical role in bone physiology

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Abstract

After it was proposed that the osteoblast lineage controlled the formation of osteoclasts, cell culture methods were developed that established this to be the case. Evidence was obtained that cytokines and hormones that promote osteoclast formation act first on osteoblast lineage cells to promote the production of a membrane-bound regulator of osteoclastogenesis. This proved to be receptor activator of NF-kB ligand (RANKL) a member of the tumor necrosis factor ligand family that acts upon its receptor RANK in the hematopoietic lineage, with interaction restricted by a decoy soluble receptor osteoprotegerin (OPG), also a product of the osteoblast lineage. The physiological roles of these factors were established through genetic and pharmacological studies, have led to a new physiology of bone, with complete revision of older ideas over the last 15 years, ultimately leading to the development of new pharmaceutical agents for bone disease.

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Acknowledgments

Work from the authors’ laboratories is supported by project grants from the National Health and Medical Research Council of Australia, and the Victorian Government OIS Program.

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The authors declare that they have no conflicts of interest.

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  1. Department of Medicine at St. Vincent’s Hospital, St. Vincent’s Institute of Medical Research and The University of Melbourne, 9 Princes St, Fitzroy, VIC, 3065, Australia

    T. John Martin & Natalie A. Sims

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Martin, T.J., Sims, N.A. RANKL/OPG; Critical role in bone physiology. Rev Endocr Metab Disord 16, 131–139 (2015). https://doi.org/10.1007/s11154-014-9308-6

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