Tumor necrosis factor-α and matrix metalloproteinase-3 production in rheumatoid arthritis synovial tissue is inhibited by blocking gap junction communication

Objective: Our aim was to establish the existence of intercellular communication through gap junctions (ICGJ) in synovial tissues and to show that gap junction communications in synovial tissue plays a role in the pathogenesis of synovitis in patients with rheumatoid arthritis (RA). Material and methods: Synovial tissues were obtained from patients with RA and osteoarthritis (OA) at the time of total knee arthroplasty. Immunohistochemistry was performed to determine the expression of Connexin 43 (Cx43) in the synovial tissues. The synovial tissues were cultured for 48 hours with various concentrations of a gap junction communication blocker (heptanol). The concentrations of TNF-α and metaloproteinases-3 (MMP-3) in the supernatants were measured using the enzyme immunoassay system (ELISA). In the preliminary stage, we had used 10 synovial tissues to determine the experimental conditions. Results: The concentrations of TNF-α and MMP-3 in supernatants decreased by adding gap junction blocker (heptanol). The expression of Cx43 was positive in the synovial tissues from the RA patients; conversely, the synovial tissues from the OA patients exhibited weak staining. Conclusions: Increased ICGP may contribute to the pathogenesis of synovitis in patients with RA because the use of a gap junction blocker inhibited the production of TNF-α and MMP-3. Thus, our findings suggest a functional role for gap junction communication in RA synovitis. It also suggests that the control of gap junction communication is a rational therapeutic target of RA synovitis.