Mechanism of bone and joint destruction in rheumatoid arthritis. Effect of mechanical stress on synovial cells.

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Synovial tissue is believe to be a main site of inflammation in rheumatoid arthritis (RA). Synovial tissue exists to line joint capsule, so the tissue is expand or relaxed in accordance with joint motion. That suggests synovial tissue is exposed to mechanical stress, however, the effect of mechanical stress on synovial tissue is not well understood. We used Flexercell system to apply expansile stress on synovial cells. Rheumatoid synovial cells seeded on type I collagen-coated flexible-bottomed well changed the shape in response to the mechanical stress. Mechanical stress induces intracellular signaling which involves small GTP protein, Rho, Rac, Ras pathway. Aminobisphosphonate, alendronate, inhibits prenylation of the small GTP protein, retards progression of bone erosion in RA patients. The RA patients who intake alendronate are tend to less susceptible to bone and joint destruction in hip and knee joints. To examine the relationship between the direction of mechanical stress and site of marginal erosion formation. More erosion is likely to be formed in ulnar side of first finger and radial side of second finger. Ulnar side of first finger and radial side of second finger are thought to be more susceptible to expansile stress. Synovial tissue lining around tendon is also susceptible to expansile mechanical stress. Cultured synovial cells differentiated to osteoclast-like cells, which formed resorption pits on dentine slice. Synovial cells derived from tendon sheath expressed MMP-1,2,3,13 and TIMP-1,2. Moreover, the cells also expressed TNF-α, IL-1β, IL-6 and RANKL. It is suggested that mechanical stress stimulates synovial cells to express pro-inflammatory cytokine and RANKL, as well as MMPs, thereby enhancing not only synovial inflammation, but joint destruction.