Role of TGF-β1 in relation to exercise-induced type I collagen synthesis in human tendinous tissue

Mechanical loading of tissue is known to influence local collagen synthesis, and microdialysis studies indicate that mechanical loading of human tendon during exercise elevates tendinous type I collagen production. Transforming growth factor-pi (TGF-beta(1)), a potent stimulator of type I collagen synthesis, is released from cultured tendon fibroblasts in response to mechanical loading. Thus TGF-beta(1) could link mechanical loading and collagen synthesis in tendon tissue in vivo. Tissue levels of TGF-beta(1) and type I collagen metabolism markers [procollagen I COOH-terminal propeptide (PICP) and COOH-terminal telopeptide of type I collagen (ICTP)] were measured by microdialysis in peritendinous tissue of the Achilles' tendon in six male volunteers before and after treadmill running (1 h, 12 km/h, 3% uphill). In addition, blood levels of TGF-beta(1), PICP, and ICTP were obtained. PICP levels increased 68 h after exercise (P < 0.05). Dialysate levels of TGF-beta(1) changed from 303 +/- 46 pg/ml (at rest) to 423 +/- 86 pg/ml 3 h postexercise. This change was nonsignificant, but the decay of tissue TGF-beta(1) after catheter insertion was markedly delayed by exercise compared with the decay seen in resting subjects. Plasma concentrations of TGF-beta(1) rose 30% in response to exercise (P < 0.05 vs. pre). Our observations indicate an increased local production of type I collagen in human peritendinous tissue in response to uphill running. Although not conclusive, changes in circulating and local TGF-beta(1), in response to exercise, suggest a role for TGF-beta(1) in mechanical regulation of local collagen type 1 synthesis in tendon-related connective tissue in vivo.