Regulation of Apoptosis and Activity of the Osteoclast

The osteoclast is the unique bone-resorbing cell that executes its duties by tight attachment to the bone, synthesis and secretion of hydrochloric acid and powerful proteases, internalization of extracellular bone matrix degradation products, and efficient migration along the bone surface. These energy-consuming activities are carried out rapidly during its short life span. An overview of osteoclast survival and bone-resorbing activity, which are critically regulated by various intracellular signaling pathways, is provided. We also discuss about the roles of several Bcl-2 family members involved in osteoclast function. While there is certainly evidence for the involvement of Bcl-2 family proteins in cell survival, we believe that some of them play important roles in osteoclastic bone resorption. The authors' insights into the regulation of apoptosis and activity of the osteoclast will provide valuable information about therapeutic approaches for the treatment of hyper-resorptive skeletal diseases.