The Osteoclast

Abstract

The osteoclast is the cell that resorbs bone. It has been known for many years that it is formed from cells of the mononuclear phagocyte system, and that its formation and function are governed by osteoblastic cells. Recently, the molecular basis for this regulation was identified: osteoblastic cells induce osteoclastic differentiation in immature mononuclear phagocytes through expression of macrophage colony-stimulating factor (M-CSF) and receptor-activator of NFкB ligand (RANKL). Osteoblastic regulation of bone resorption is assisted through secretion of an inhibitor, osteoprotegerin (OPG), a soluble (decoy) receptor for RANKL. Transforming growth factor beta (TGF-β), which is present in bone matrix in large amounts, is also essential for osteoclast formation, at least in vitro. Surprisingly, TNF-α can substitute for and is strongly synergistic with RANKL for osteoclast-induction. TNF-α is widely expressed, and RANKL can also be present in situations that are not associated with osteoclast formation, so that the presence of large quantities of TGF-β in bone matrix might explain why osteoclast formation is essentially confined to the bone microenvironment. In this review, recent data concerning the mechanisms underlying the induction of osteoclastic differentiation and function are described, together with recent findings concerning the mechanisms through which osteoclasts adhere to and resorb bone. Several of these mechanisms are currently being exploited for the development of novel therapies for diseases, such as osteoporosis, that are caused by excessive bone resorption.KeywordsOsteoclastOsteoblastRANKLTNF-?TGF-?Bone