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Joint-protective effects of compound K, a major ginsenoside metabolite, in rheumatoid arthritis: in vitro evidence

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Abstract

Regulatory expression of matrix metalloproteinases (MMPs) and osteoclastogenesis is implicated in the process of joint destruction in rheumatoid arthritis (RA). Although several reports suggested the anti-arthritic effects of ginseng saponins, it has not been investigated whether the most absorbable ginsenoside, compound K (CK), has a joint-protective action. We here investigated the effect of CK (0–5 μM) on TNF-α-induced MMP-1, MMP-3, and MMP-13 and TIMP-1 production from RA fibroblast-like synoviocytes (FLS) and determined the inhibitory effect of CK on osteoclastogenesis from RAW264.7 cells co-cultured with RA-FLS and from human CD14+ monocytes. The effect of CK on NF-κB, nuclear factor of activated T cells c1 (NFATc1), and mitogen-activated protein kinases pathways were evaluated using immunoblotting or specific inhibitors. CK significantly inhibited MMP-1 and MMP-3 productions from RA-FLS in a concentration-dependent manner through suppressing the JNK and ERK pathways. In the co-culture system of TNF-α-stimulated RA-FLS and RAW264.7 cells, CK dose-dependently reduced receptor activator of NF-κB ligand (RANKL) expression in the RA-FLS and inhibited the formation of tartrate-resistant acid phosphatase (TRAP)-positive osteoclast-like cells. Furthermore, CK significantly inhibited soluble RANKL-induced osteoclastogenesis or osteoclast activity in RAW264.7 cells and human CD14+ monocytes through inhibition of RANKL-induced IκBα degradation and NFATc1 expression. In conclusion, our results increase the understanding of the molecular mechanisms of the joint-protective effects of CK in RA. The characteristic actions of CK provide in vitro evidence for its potential utility in RA therapy.

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Acknowledgments

This study was supported by a grant of the Korea Health technology R&D Project, Ministry of Health & Welfare, Republic of Korea. (A090933).

Conflict of interest

Lee, E.B. is a consultant for Pfizer Inc. The other authors declare to have no competing interests.

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Authors and Affiliations

  1. Department of Internal Medicine, Seoul National University Bundang Hospital, 166 Gumi-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-707, Korea

    Yong Seok Choi, Eun Ha Kang & Yun Jong Lee

  2. Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea

    Eun Young Lee, Eun Bong Lee & Yeong Wook Song

  3. Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea

    Eun Young Lee, Eun Bong Lee & Yun Jong Lee

  4. Department of Orthopedic Surgery, Seoul National University Bundang Hospital, Seongnam-si, Korea

    Hyun Sik Gong

  5. Metabolab Inc., Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea

    Heun Soo Kang

  6. Department of Internal Medicine, Seoul National University Borame Medical Center, Seoul, Korea

    Kichul Shin

  7. WCU Department of Molecular Medicine and Biopharmaceutical Sciences, Medical Research Institute, Seoul National University College of Medicine, Seoul, Korea

    Yeong Wook Song

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  1. Yong Seok Choi
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Correspondence to Yun Jong Lee.

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Choi, Y.S., Kang, E.H., Lee, E.Y. et al. Joint-protective effects of compound K, a major ginsenoside metabolite, in rheumatoid arthritis: in vitro evidence. Rheumatol Int 33, 1981–1990 (2013). https://doi.org/10.1007/s00296-013-2664-9

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  • DOI: https://doi.org/10.1007/s00296-013-2664-9

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