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

被引：53

作者：

Kim, Ju-Young ^{[1
]}

Cheon, Yoon-Hee ^{[2
]}

Oh, Hyun Mee ^{[3
]}

Rho, Mun Chual ^{[3
]}

Erkhembaatar, Munkhsoyol ^{[4
]}

Kim, Min Seuk ^{[4
,5
]}

Lee, Chang Hoon ^{[5
,6
]}

Kim, Jeong Joong ^{[2
,5
]}

Choi, Min Kyu ^{[2
]}

Yoon, Kwon-Ha ^{[1
,7
]}

Lee, Myeung Su ^{[1
,5
,6
]}

Oh, Jaemin ^{[1
,2
,5
]}

机构：

[1] Wonkwang Univ, Imaging Sci Based Lung & Bone Dis Res Ctr, Iksan 570749, Jeonbuk, South Korea

[2] Wonkwang Univ, Sch Med, Dept Anat, Iksan 570749, Jeonbuk, South Korea

[3] Korea Res Inst Biosci & Biotechnol, Biomat Res Inst, Bioind Proc Res Ctr, Jeongeup 580185, Jeonbuk, South Korea

[4] Wonkwang Univ, Sch Dent, Dept Oral Physiol, Iksan 570749, Jeonbuk, South Korea

[5] Wonkwang Univ, Inst Skeletal Dis, Iksan 570749, Jeonbuk, South Korea

[6] Wonkwang Univ, Div Rheumatol, Dept Internal Med, Iksan 570749, Jeonbuk, South Korea

[7] Wonkwang Univ, Sch Med, Dept Radiol, Iksan 570749, Jeonbuk, South Korea

来源：

BONE | 2014年 / 60卷

关键词：

Osteoclast; Oleanolic acid acetate; PLC gamma 2; Calcium oscillation; NFATc1; SPONTANEOUSLY HYPERTENSIVE-RATS; PHOSPHOLIPASE-C-GAMMA; ANGULARIS SEED COATS; HOT-WATER EXTRACT; VIGNA-ANGULARIS; RECEPTOR ACTIVATOR; DIABETIC-RATS; IMMUNE-SYSTEM; CELLS; OSTEOIMMUNOLOGY;

D O I：

10.1016/j.bone.2013.12.013

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：104 / 111

页数：8