MMP-1, IL-1beta, and COX-2 mRNA expression is modulated by static load in rabbit flexor tendons

Tendon cells respond to their mechanical environment by synthesizing and degrading the surrounding matrix. This study examined how expression of genes associated with tendon degeneration is affected by static loads. Forty flexor tendons from 10 New Zealand White rabbits were harvested and secured in a tissue loading system. A static load of 0, 2, 4, or 6 MPa was applied to tendons for 20 h. MMP-1, IL-1beta, COX-2, GAPDH, and 18s mRNA expression was measured by qRT-PCR. MMP-1 expression in tendons loaded to 6 MPa was significantly increased 259% compared to tendons loaded to 4 MPa. Relative to a 0 MPa load, IL-1beta expression was inhibited with load at 4 MPa (48%) while COX-2 expression was increased at 6 MPa (219%). A polynomial regression analysis found a significant positive correlation between creep and expression of MMP-1 (R(2) = 0.53, p < 0.001) and IL-1beta (R(2) = 0.55, p < 0.001). The results of this study indicate that moderate load inhibits IL-1beta and high load stimulates COX-2 relative to stress shielding. MMP-1 expression is up-regulated with high loads compared to moderate loads. The correlation between creep and expression suggests that the pathway for MMP-1 and IL-1beta expression, leading eventually to tendon degeneration, may be regulated by the biomechanical factor creep.