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Role of TGF-₁ in relation to exercise-induced type I collagen synthesis in human tendinous tissue

Sports Medicine Research Unit, Department of Rheumatology H, Bispebjerg Hospital, DK-2400 Copenhagen, Denmark

Submitted 23 April 2003 ; accepted in final form 8 August 2003

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-₁ (TGF-₁), a potent stimulator of type I collagen synthesis, is released from cultured tendon fibroblasts in response to mechanical loading. Thus TGF-₁ could link mechanical loading and collagen synthesis in tendon tissue in vivo. Tissue levels of TGF-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-₁, PICP, and ICTP were obtained. PICP levels increased 68 h after exercise (P < 0.05). Dialysate levels of TGF-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-₁ after catheter insertion was markedly delayed by exercise compared with the decay seen in resting subjects. Plasma concentrations of TGF-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-₁, in response to exercise, suggest a role for TGF-₁ in mechanical regulation of local collagen type I synthesis in tendon-related connective tissue in vivo.

extracellular matrix; tendon; mechanical loading; transforming growth factor-₁

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