Increased Serum TNF-Alpha and Matrix Metalloproteinase-2 are Associated With Grip Strength Declines and Tissue Degeneration in a Rat Model of Overuse

Abstract

We have shown that continued performance of repetitive tasks induces grip strength declines despite resolution of systemic inflammation. We hypothesize this is due to underlying tissue degeneration. Here, we assessed long term performance (18 weeks) of a high-repetition, low-force (HRLF) task in a rat model of reaching and grasping. We observed reduced grip strength immediately after training, and persistent grip strength declines in reach limbs of HRLF rats. Several inflammatory cytokines increased in serum of 6- and 12-week HRLF rats, e.g. tumor necrosis factor alpha (TNF-alpha). TNF- alpha was also increased in reach limb muscles and tendons at similar time points. A serum analyte of collagen degradation (matrix metalloproteinase-2, MMP2) was increased in serum of 18-week HRLF rats. MMP2 and several other MMPs, as well as two fibrogenic proteins (CTGF and TGFB1), were increased in 18-week HRLF tendons, which also showed histological signs of pathology. Thus, motor declines were associated earlier with tissue inflammation but later with tendon degenerative changes. Assaying for TNF- alpha and MMP2 provided important insights into the stages of inflammation and degradation in this model.