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

• Published in: Bone (New York, N.Y.) Vol. 60; pp. 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: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.03.2014; Elsevier
• Subjects: Biological and medical sciences; Calcium oscillation; Cell differentiation, maturation, development, hematopoiesis; Cell physiology; Diseases of the osteoarticular system; Fundamental and applied biological sciences. Psychology; Medical sciences; Molecular and cellular biology; NFATc1; Oleanolic acid acetate; Osteoclast; Osteoporosis. Osteomalacia. Paget disease; PLCγ2; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Calcium oscillation; Osteoclast; NFATc1; PLCγ2; Oleanolic acid acetate; Calcium; Diseases of the osteoarticular system; Rodentia; Cell differentiation; Vertebrata; Mammalia; Mouse; Animal; Morphology; Oscillation; Osteopenia
• ISSN: 8756-3282; 1873-2763
• DOI: 10.1016/j.bone.2013.12.013

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-κB 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 Cγ2 (PLCγ2) 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 PLCγ2-Ca2+-NFATc1 signaling in vitro and suppressed inflammatory bone loss in vivo. •We first isolated oleanolic acid acetate (OAA), a triterpenoid compound, from Vigna angularis (azuki bean) to discover anti-bone resorptive agents.•Our data demonstrate for the first time that OAA can suppress osteoclastogenesis both in vitro and in vivo.•OAA inhibited RANKL-mediated osteoclastogenesis via PLCγ2-Ca2+-NFATc1 signaling in vitro.•OAA demonstrated marked attenuation of lipopolysaccharide-induced bone erosion based on micro-computed tomography and histologic analysis of femurs.•OAA could be a potential therapeutic candidate for treating osteoclast-related diseases such as osteoporosis.