Chlorogenic Acid Inhibits of 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
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概要
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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 G. 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 RANKL (receptor activator of NF-κB ligand)-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, ERK, and IκB, and IκB 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 osteoclast-related diseases with inflammatory bone destruction.
著者
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Oh Jaemin
Department Of Anatomy Wonkwang University
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Lee Cheol
Department Of Chemical Engineering Hanyang University
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Oh Jaemin
Department of Anatomy, School of Medicine, Wonkwang University School of Medicine
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Oh Hyun
Bioindustrial Process Research Center, Bio-Materials Research Institute, Korea Research Institute of Bioscience and Biotechnology
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Kwak Sung
Department of Anatomy, School of Medicine, Wonkwang University School of Medicine
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Kim Ju-Young
Imaging Science-based Lung and Bone Diseases Research Center, Wonkwang University School of Medicine
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So Hong-Seob
Center for Metabolic Function Regulation, Department of Microbiology, Wonkwang University School of Medicine
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Lee Myeung
Imaging Science-based Lung and Bone Diseases Research Center, Wonkwang University School of Medicine
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Rho Mun
Bioindustrial Process Research Center, Bio-Materials Research Institute, Korea Research Institute of Bioscience and Biotechnology
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Lee Cheol
Department of Anesthesiology and Pain Medicine, Wonkwang University School of Medicine
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