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Molecular regulation of osteoclast activity

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Abstract

Osteoclasts are multinucleated cells derived from hematopoietic precursors that are primarily responsible for the degradation of mineralized bone during bone development, homeostasis and repair. In various skeletal disorders such as osteoporosis, hypercalcemia of malignancy, tumor metastases and Paget’s disease, bone resorption by osteoclasts exceeds bone formation by osteoblasts leading to decreased bone mass, skeletal fragility and bone fracture. The overall rate of osteoclastic bone resorption is regulated either at the level of differentiation of osteoclasts from their monocytic/macrophage precursor pool or through the regulation of key functional proteins whose specific activities in the mature osteoclast control its attachment, migration and resorption. Thus, reducing osteoclast numbers and/or decreasing the bone resorbing activity of osteoclasts are two common therapeutic approaches for the treatment of hyper-resorptive skeletal diseases. In this review, several of the key functional players involved in the regulation of osteoclast activity will be discussed.

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Acknowledgments

We thank Dr. C. Itzstein for critically reading this manuscript and Lynn Neff for providing confocal images. This work was funded in part by grants from the National Institutes of Health to R. Baron (DE04724 and AR42927) and by a Pilot and Feasibility Grant from the Yale Core Center for Musculoskeletal Disorders to A. Bruzzaniti.

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  1. Departments of Orthopaedics and Cell Biology, Yale University School of Medicine, New Haven, CT, 06510, USA

    Angela Bruzzaniti & Roland Baron

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Correspondence to Angela Bruzzaniti.

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Bruzzaniti, A., Baron, R. Molecular regulation of osteoclast activity. Rev Endocr Metab Disord 7, 123–139 (2006). https://doi.org/10.1007/s11154-006-9009-x

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