Oleanolic acid acetate inhibits osteoclast differentiation by downregulating PLCγ2-Ca2+-NFATc1 signaling, and suppresses bone loss in mice

Owing to their potential pharmacological activities in human disease, natural plant-derived compounds have recently become the focus of increased research interest. In this study, we first isolated oleanolic acid acetate (OAA), a triterpenoid compound, from Vigna angularis (azuki bean) to discover anti-bone resorptive agents. Many studies have identified and described the various medicinal effects of V. angularis extract. However, the pharmacological effect of OAA-derived V. angularis extract, particularly the effect on osteoclastogenesis, is not known. Therefore, we investigated the effect and mechanism of OAA in receptor activator of nuclear factor-KB ligand (RANKL)-induced osteodastogenesis. OAA inhibited RANKL-induced osteoclast differentiation in bone marrow macrophages (BMMs) without any evidence of cytotoxicity. Interestingly, OAA significantly inhibited Btk phosphorylation, phospholipase C gamma 2 (PLC gamma 2) phosphorylation, calcium ion (Ca2+) oscillation, and nuclear factor of activated T cell cl (NFATc1) expression in RANKL-stimulated BMMs, but did not affect RANKL-induced mitogen-activated protein kinase. OAA also inhibited the bone-resorbing activity of mature osteoclasts. Furthermore, mice treated with QAA demonstrated marked attenuation of lipopolysaccharide-induced bone erosion based on micro-comPuted tomography and histologic analysis of femurs. Taken together, the results suggested that OAA inhibited RANKL-mediated osteoclastogenesis via PLC gamma 2-Ca2+-NFATc1 signaling in vitro and suppressed inflammatory bone loss in vivo. (C) 2013 Published by Elsevier Inc.