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IL-18 Upregulates the Production of Key Regulators of Osteoclastogenesis from Fibroblast-Like Synoviocytes in Rheumatoid Arthritis

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Abstract

Recent data have demonstrated the importance of IL-18 in the induction and perpetuation of chronic inflammation in experimental arthritis. The aim of the present study was to elucidate whether IL-18 has any indirect effects on osteoclastogenesis by regulating the production of molecules from fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA). Human FLS were isolated from RA synovial tissue and cultured in vitro for three to five passages. The expression of IL-18 receptor was determined by RT-PCR. The levels of soluble receptor activator of nuclear factor κB ligand (RANKL), osteoprotegerin (OPG), macrophage colony-stimulating factor (M-CSF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) in culture supernatants were determined by ELISA. Membrane-bound RANKL expression was analyzed by flow cytometry. Both α and β chains of IL-18 receptor were confirmed in cultured FLS. IL-18 upregulated membrane-bound RANKL expression and soluble RANKL production by FLS in both time- and dose-dependent manners. In addition, IL-18 enhanced production of M-CSF, GM-CSF, and OPG from cultured FLS in a dose-dependent manner. IL-18 also increased the ratio of RANKL/OPG, suggesting that the net effect of IL-18 on FLS favors for the induction of osteoclast formation and bone resorption. In conclusion, IL-18 upregulates the production of key regulators of osteoclastogenesis from FLS in RA.

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Acknowledgments

This study was supported by the grants from National Natural Science Foundation of China (Nos. 30972729 and 81172852).

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All authors have no conflicts of interest.

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Authors and Affiliations

  1. Changzheng Hospital, Second Military Medical University, Shanghai, China

    Wei Zhang & Xiao-Liang Cong

  2. Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai, 200433, People’s Republic of China

    Yang-Hua Qin, Zheng-Wen He & Sheng-Ming Dai

  3. Department of Rheumatology, Shanghai Guanghua Hospital, 540 Xinhua Road, Shanghai, 200052, People’s Republic of China

    Dong-Yi He

Authors
  1. Wei Zhang
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  2. Xiao-Liang Cong
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  3. Yang-Hua Qin
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Correspondence to Dong-Yi He or Sheng-Ming Dai.

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Drs. Wei Zhang and Xiao-Liang Cong contributed equally to this work.

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Zhang, W., Cong, XL., Qin, YH. et al. IL-18 Upregulates the Production of Key Regulators of Osteoclastogenesis from Fibroblast-Like Synoviocytes in Rheumatoid Arthritis. Inflammation 36, 103–109 (2013). https://doi.org/10.1007/s10753-012-9524-8

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  • DOI: https://doi.org/10.1007/s10753-012-9524-8

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