Silencing the expression of connexin 43 decreases inflammation and joint destruction in experimental arthritis.

Shinji Tsuchida, Yuji Arai, Tsunao Kishida, Kenji A Takahashi, Kuniaki Honjo, Ryu Terauchi, Hiroaki Inoue, Ryo Oda, Osam Mazda, Toshikazu Kubo

Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.

Journal of orthopaedic research : official publication of the Orthopaedic Research Society 2013 Apr

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The objective of the present study was to determine whether the expression of connexin 43 (Cx43) effected on inflammatory conditions in rat fibroblast-like synoviocytes (FLS) and on rat model of rheumatoid arthritis (RA). The expression of Cx43 in rat FLS stimulated with lipopolysaccharide (LPS) was confirmed by real-time reverse transcriptase polymerase chain reaction (RT-PCR). The effects of small-interfering RNA targeting Cx43 (siCx43) on pro-inflammatory cytokines and chemokine were assessed by real-time RT-PCR and enzyme-linked immunosorbent assay (ELISA). The therapeutic and side effects of siCx43 in a rat model of collagen-induced arthritis (CIA) were examined by in vivo electroporation method. LPS markedly enhanced Cx43 gene expression in rat FLS, with transfection of siCx43 suppressing the over-expression of pro-inflammatory cytokines and the chemokine. Treatment of CIA rats with siCx43 significantly ameliorated paw swelling, and significantly reduced histological arthritis scores and radiographic scores. In histological appearance of rat ankle joints, siCx43 treatment significantly decreased the number of tartrate-resistant acid phosphatase (TRAP)-positive (osteoclast-like) cells. These findings indicated that siCx43 had anti-inflammatory effects in rat FLS and efficiently inhibited the development of CIA. Cx43 may play an important role in the pathophysiology of RA, and may be a potential target molecule for novel RA therapies. Copyright © 2012 Orthopaedic Research Society.

Citation

Shinji Tsuchida, Yuji Arai, Tsunao Kishida, Kenji A Takahashi, Kuniaki Honjo, Ryu Terauchi, Hiroaki Inoue, Ryo Oda, Osam Mazda, Toshikazu Kubo. Silencing the expression of connexin 43 decreases inflammation and joint destruction in experimental arthritis. Journal of orthopaedic research : official publication of the Orthopaedic Research Society. 2013 Apr;31(4):525-30