Effects and mechanisms of microenvironmental acidosis on osteoclast biology

Due to continuous bone remodeling, the bone tissue is dynamic and constantly being updated. Bone remodeling is precisely regulated by the balance between osteoblast-induced bone formation and osteoclast-induced bone resorption. As a giant multinucleated cell, formation and activities of osteoclasts are regulated by macrophage colony-stimulating factor (M-CSF), receptor activator of nuclear factor-kappaB ligand (RANKL), and by pathological destabilization of the extracellular microenvironment. Microenvironmental acidosis, as the prime candidate, is a driving force of multiple biological activities of osteoclast precursor and osteoclasts. The mechanisms involved in these processes, especially acid-sensitive receptors/channels, are of great precision and complicated. Recently, remarkable progress has been achieved in the field of acid-sensitive mechanisms of osteoclasts. It is important to elucidate the relationship between microenvironmental acidosis and excessive osteoclasts activity, which will help in understanding the pathophysiology of diseases that are associated with excess bone resorption. This review summarizes physiological consequences and in particular, potential mechanisms of osteoclast precursor or osteoclasts in the context of acidosis microenvironments.