Chlorogenic acid inhibits osteoclast differentiation and bone resorption by down-regulation of receptor activator of nuclear factor kappa-B ligand-induced nuclear factor of activated T cells c1 expression = 클로로제닉 산의 파골세포분화 및 골흡수억제 활성

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Title
Chlorogenic acid inhibits osteoclast differentiation and bone resorption by down-regulation of receptor activator of nuclear factor kappa-B ligand-induced nuclear factor of activated T cells c1 expression = 클로로제닉 산의 파골세포분화 및 골흡수억제 활성
Author(s)
S C Kwak; C Lee; J Y Kim; Hyun-Mee Oh; H S So; M S Lee; Mun Chual Rho; J Oh
Bibliographic Citation
Biological & Pharmaceutical Bulletin, vol. 36, no. 11, pp. 1779-1786
Publication Year
2013
Abstract
Excessive osteoclastic bone resorption plays a critical role in inflammation-induced bone loss such as rheumatoid arthritis and periodontal bone erosion. Therefore, identification of osteoclast targeted-agents may be a therapeutic approach to the treatment of pathological bone loss. In this study, we isolated chlorogenic acid (CGA) from fructus of Gardenia jasminoides to discover anti-bone resorptive agents. CGA is a polyphenol with anti-inflammatory and anti-oxidant activities, however, its effects on osteoclast differentiation is unknown. Thus, we investigated the effect of CGA in receptor activator of nuclear factor-kappa B (NF-κB) ligand (RANKL)-induced osteoclast differentiation and RANKL signaling. CGA dose-dependently inhibited RANKL-mediated osteoclast differentiation in bone marrow macrophages (BMMs) without any evidence of cytotoxicity. CGA inhibited the phosphorylation of p38, Akt, extracellular signal-regulated kinase (ERK), and inhibitor of nuclear factor-kappa B (IeB), and IeB degradation by RANKL treatment. CGA suppressed the mRNA expression of nuclear factor of activated T cells c1 (NFATc1), TRAP and OSCAR in RANKL-treated bone marrow macrophages (BMMs). Also, overexpression of NFATc1 in BMMs blocked the inhibitory effect of CGA on RANKL-mediated osteoclast differentiation. Furthermore, to evaluate the effects of CGA in vivo, lipopolysaccharide (LPS)-induced bone erosion study was carried out. CGA remarkably attenuated LPS-induced bone loss based on micro-computed tomography and histologic analysis of femurs. Taken together, our findings suggest that CGA may be a potential treatment option for osteoclastrelated diseases with inflammatory bone destruction.
Keyword
Chlorogenic acidDifferentiationLipopolysaccharide-induced bone destructionNuclear factor of activated T cells c1OsteoclastReceptor activator of nuclear factor kappa-B ligand
ISSN
0918-6158
Publisher
Pharmaceutical Soc Japan
DOI
http://dx.doi.org/10.1248/bpb.b13-00430
Type
Article
Appears in Collections:
Jeonbuk Branch Institute > Immunoregulatory materials Research Center > 1. Journal Articles
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