Involvement of the mitogen-activated protein kinase signalling pathway in osteoprotegerin-induced inhibition of osteoclast differentiation and maturation

Abstract

The present study aimed to determine whether the mitogen-activated protein kinase (MAPK) signaling pathway is involved in the osteoprotegerin (OPG)-mediated inhibition of osteoclast differentiation and maturation. RAW264.7 cells were incubated with macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL) to stimulate osteoclastogenesis and treated with various concentrations of OPG, an inhibitor of osteoclast differentiation. The differentiation and activation of osteoclasts were monitored by tartrate-resistant acid phosphatase staining and bone resorption assays. The phosphorylation levels of p38-MAPK, c-Jun N-terminal kinase (JNK)-MAPK and extracellular signal-regulated kinase (ERK)-MAPK in the different treatment groups were determined by western blot analysis. The results confirmed that M-CSF + RANKL stimulated the differentiation and activation of osteoclasts as well as the phosphorylation of p38-MAPK, JNK-MAPK and ERK-MAPK in osteoclasts, which was attenuated by OPG treatment. These findings indicated that the MAPK signaling pathway is involved in the regulation of osteoclastogenesis and in the OPG-mediated inhibition of osteoclast differentiation and activation.