Review
Regulation of apoptosis in osteoclasts and osteoblastic cells

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Abstract

In postnatal life, the skeleton undergoes continuous remodeling in which osteoclasts resorb aged or damaged bone, leaving space for osteoblasts to make new bone. The balance of proliferation, differentiation, and apoptosis of bone cells determines the size of osteoclast or osteoblast populations at any given time. Bone cells constantly receive signals from adjacent cells, hormones, and bone matrix that regulate their proliferation, activity, and survival. Thus, the amount of bone and its microarchitecture before and after the menopause or following therapeutic intervention with drugs, such as sex hormones, glucocorticoids, parathyroid hormone, and bisphosphonates, is determined in part by effects of these on survival of osteoclasts, osteoblasts, and osteocytes. Understanding the mechanisms and regulation of bone cell apoptosis will enhance our knowledge of bone cell function and help us to develop better therapeutics for the management of osteoporosis and other bone diseases.

Section snippets

Apoptosis and its regulation

Apoptosis is controlled by two distinct signaling pathways, one initiated by death receptors, members of the TNF receptor family with an intracellular death domain, and the other regulated by Bcl-2 family proteins, which involves mitochondrial release of cytochrome c. Both pathways activate a family of proteolytic enzymes called caspases that induce the morphological features of apoptosis by cleaving specific substrates (Fig. 1).

Death receptors. Death receptors (DR) include CD95 (Fas/APO-1) and

Summary

Our understanding of the molecular regulation of osteoclast and osteoblast formation, differentiation, and survival has increased dramatically in the past decade, largely from observation and study of the phenotype and cells from transgenic and knockout mice. It is now clear that the life span of osteoclasts, osteoblasts, and osteocytes is an important determinant of bone mass and strength. Furthermore, some of the drugs used to treat or prevent common bone diseases mediate their effects by

Acknowledgments

The authors thank Aihua Dai, Qian Zhang, Zhenqiang Yao, Teruhito Yamashita, and Raul Badell for technical assistance, Bianai Feng for histology, and Ildiko Nagy for secretarial assistance. Some of the work described was supported in part by Grants from the NIH (AR43510 and AR41336 to B.F.B.; and AR48697 to L. Xing).

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