Osteoclasts-key players in skeletal health and disease

The differentiation of osteoclasts (OCs) from early myeloid progenitors is a tightly regulated process that is modulated by a variety of mediators present in the bone microenvironment. Once generated, the function of mature OCs depends on cytoskeletal features controlled by an a_vβ₃-containing complex at the bone-apposed membrane and the secretion of protons and acid-protease cathepsin K. OCs also have important interactions with other cells in the bone microenvironment, including osteoblasts and immune cells. Dysregulation of OC differentiation and/or function can cause bone pathology. In fact, many components of OC differentiation and activation have been targeted therapeutically with great success. However, questions remain about the identity and plasticity of OC precursors and the interplay between essential networks that control OC fate. In this review, we summarize the key principles of OC biology and highlight recently uncovered mechanisms regulating OC development and function in homeostatic and disease states.