Oleanolic acid acetate inhibits osteoclast differentiation by downregulating PLC gamma 2-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 a...

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Published in:Bone (New York, N.Y.) N.Y.), 2014-03, Vol.60, p.104-111
Main Authors: Kim, Ju-Young, Cheon, Yoon-Hee, Oh, Hyun Mee, Rho, Mun Chual, Erkhembaatar, Munkhsoyol, Kim, Min Seuk, Lee, Chang Hoon, Kim, Jeong Joong, Choi, Min Kyu, Yoon, Kwon-Ha, Lee, Myeung Su, Oh, Jaemin
Format: Article
Language:English
Subjects:
Vigna angularis
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Summary: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- Kappa B ligand (RANKL)-induced osteoclastogenesis. 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 c1 (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 OAA 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.
ISSN:8756-3282
DOI:10.1016/j.bone.2013.12.013