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Distinct expression of mast cell tryptase and protease activated receptor-2 in synovia of rheumatoid arthritis and osteoarthritis

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Abstract

The objective of this study is to examine the differential expression of mast cell tryptase and its receptor, protease-activated receptor-2 (PAR-2), in the synovium and synovial fluid of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Biochemical and immunohistochemical analyses were performed to determine whether the trypsin-like protease in the synovium is identical to mast cell tryptase. The effects of mast cell tryptase on the proliferation of synovial fibroblast-like cells (SFCs) and the release of IL-8 thereof were evaluated by the [3H]-thymidine incorporation and ELISA, respectively. The trypsin-like protease in the synovium of RA patients was identical to human mast cell tryptase, which was composed of two subunits: 33 and 34 kDa. The 33- and 34-kDa proteins are different glycosylated forms of the 31-kDa protein, which was unglycosylated. Mast cell tryptase activity in RA synovial fluid was significantly higher than that in OA synovial fluid, while their activities and expression in the synovium were similar. Expression of PAR-2 mRNA in the synovium was higher in RA than in OA. Mast cell tryptase containing the unglycosylated 31-kDa subunit was the predominant form in synovial fluid. RA patients had higher amounts of this subunit in their synovial fluid than OA patients. Mast cell tryptase and PAR-2 activating peptide stimulated the proliferation of SFCs and release of IL-8 from these cells. Mast cell tryptase secretion into RA synovial fluid is higher than OA synovial fluid. Mast cell tryptase in synovial fluid stimulates the proliferation of SFCs and the release of pro-inflammatory cytokines via PAR-2, which may contribute to exacerbation of synovitis in RA.

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Acknowledgments

We gratefully acknowledged Yukio Higuchi M.D. and Yoshiteru Kawasaki M.D. (Tokushima Prefectural Central Hospital) for collecting the control specimens, and Yuichi Ikeda M.D. and Sachiko Kawano Ph.D. for excellent technical assistance. Financial support for this study was provided by a Grant-in-Aid for Scientific Research (C).

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Authors and Affiliations

  1. Department of Orthopedics, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15 Kuramoto, Tokushima, 770-8503, Japan

    Shunji Nakano, Takuya Mishiro, Shigeyuki Takahara, Hiromichi Yokoi, Daisuke Hamada, Kiminori Yukata, Yoichiro Takata, Tomohiro Goto, Hiroshi Egawa & Natsuo Yasui

  2. Department of Internal Medicine, Hakuai Kinen Hospital, Tokushima, 770-8023, Japan

    Susumu Yasuoka

  3. Department of Nutrition, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, 770-8503, Japan

    Harumi Furouchi, Katsuya Hirasaka & Takeshi Nikawa

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  1. Shunji Nakano
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  2. Takuya Mishiro
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  14. Natsuo Yasui
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Correspondence to Natsuo Yasui.

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Nakano, S., Mishiro, T., Takahara, S. et al. Distinct expression of mast cell tryptase and protease activated receptor-2 in synovia of rheumatoid arthritis and osteoarthritis. Clin Rheumatol 26, 1284–1292 (2007). https://doi.org/10.1007/s10067-006-0495-8

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  • DOI: https://doi.org/10.1007/s10067-006-0495-8

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