Oleanolic acid acetate inhibits osteoclast differentiation by downregulating PLCgamma2-Ca2+-NFATc1 signaling, and suppresses bone loss in mice = 파골세포 분화와 마우스에서 골파괴를 억제하는 올레놀린산

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Title
Oleanolic acid acetate inhibits osteoclast differentiation by downregulating PLCgamma2-Ca2+-NFATc1 signaling, and suppresses bone loss in mice = 파골세포 분화와 마우스에서 골파괴를 억제하는 올레놀린산
Author(s)
J Y Kim; Y H Cheon; Hyun-Mee Oh; Mun Chual Rho; M Erkhembaatar; M S Kim; C H Lee; J J Kim; M K Choi; K H Yoon; M S Lee; J Oh
Bibliographic Citation
Bone, vol. 60, pp. 104-111
Publication Year
2014
Abstract
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
Keyword
Calcium oscillationNFATc1Oleanolic acid acetateOsteoclastPLCγ2
ISSN
8756-3282
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.bone.2013.12.013
Type
Article
Appears in Collections:
Jeonbuk Branch Institute > Immunoregulatory materials Research Center > 1. Journal Articles
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