Promotion of osteoclast differentiation and activation in spite of impeded osteoblast-lineage differentiation under acidosis: effects of acidosis on bone metabolism

Abstract

The acidosis that accompanies many diseases and pathological conditions can promote osteoclast formation and activation. Acidosis mainly acts on the last phase of osteoclast formation to generate large osteoclasts and promote bone resorption. There are several acid-sensing mechanisms, among which transient receptor potential (TRP) channels and G protein-related receptors have been focused on. TRPV4 channels appear to be, at least partly, implicated in acidosis-promoted large osteoclast formation. Other TRP channels including TRPV1 and TRPV2 might be components of the acid-sensing machinery. Several reports suggest the involvement of ovarian cancer G protein-coupled receptor 1 (OGR1), a G-protein-related acid sensor, in receptor activator of nuclear factor kappa-B ligand (RANKL) expression via cyclooxygenase-2 (COX-2). On the other hand, acidosis impairs osteoblast differentiation, which is further impeded in the presence of inflammatory cytokines.