Chlorogenic acid inhibits osteoclast differentiation and bone resorption by down-regulation of receptor activator of nuclear factor κ-B ligand-induced nuclear factor of activated T cells c1 expression

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  • Kwak Sung Chul
    Department of Anatomy, School of Medicine, Wonkwang University School of Medicine Center for Metabolic Function Regulation, Department of Microbiology, Wonkwang University School of Medicine
  • Lee Cheol
    Department of Anesthesiology and Pain Medicine, Wonkwang University School of Medicine
  • Kim Ju-Young
    Imaging Science-based Lung and Bone Diseases Research Center, Wonkwang University School of Medicine
  • Oh Hyun Mee
    Bioindustrial Process Research Center, Bio-Materials Research Institute, Korea Research Institute of Bioscience and Biotechnology
  • So Hong-Seob
    Center for Metabolic Function Regulation, Department of Microbiology, Wonkwang University School of Medicine
  • Lee Myeung Su
    Imaging Science-based Lung and Bone Diseases Research Center, Wonkwang University School of Medicine Institute for Skeletal Disease, Wonkwang University School of Medicine Department of Rheumatology, Wonkwang University School of Medicine
  • Rho Mun Chual
    Bioindustrial Process Research Center, Bio-Materials Research Institute, Korea Research Institute of Bioscience and Biotechnology
  • Oh Jaemin
    Department of Anatomy, School of Medicine, Wonkwang University School of Medicine Imaging Science-based Lung and Bone Diseases Research Center, Wonkwang University School of Medicine Institute for Skeletal Disease, Wonkwang University School of Medicine

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  • 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

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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 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 (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.

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