title: Silencing the expression of connexin 43 decreases inflammation and joint destruction in experimental arthritis.
abstract: 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.
authors.affiliation: Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Tsuchida
authors.forename: Yuji
authors.initials: Y
authors.lastname: Arai
authors.forename: Tsunao
authors.initials: T
authors.lastname: Kishida
authors.forename: Kenji A
authors.initials: KA
authors.lastname: Takahashi
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Honjo
authors.forename: Ryu
authors.initials: R
authors.lastname: Terauchi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Inoue
authors.forename: Ryo
authors.initials: R
authors.lastname: Oda
authors.forename: Osam
authors.initials: O
authors.lastname: Mazda
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Kubo
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism / Q000473:pathology*; D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology; D024043:Collagen Type II / Q000633:toxicity; D018031:Connexin 43 / Q000096:biosynthesis*; D016207:Cytokines / Q000096:biosynthesis; D008297:Male; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D013583:Synovial Membrane / Q000166:cytology / Q000378:metabolism*
chemical_list: D024043:Collagen Type II; D018031:Connexin 43; D016207:Cytokines; D034741:RNA, Small Interfering