Several tissue types react to mechanical stress by increasing the synthesis of type I collagen, and recent microdialysis studies indicate that mechanical loading during exercise can similarly influence type I collagen production in tendon tissue (Langberg et al. 1999). However, the link between mechanical loading and type I collagen synthesis in tendon is yet unknown.
Studies indicate that transforming growth factor-β (TGF-β), which potently induces type I collagen synthesis in fibroblasts, could connect mechanical loading to type I collagen production. Cultured tendon fibroblasts increase the expression of TGF-β in response to mechanical stress and mechanically induced type I collagen synthesis has been found to be dependent on TGF-β activity in cardiac fibroblasts and intestinal smooth muscle cells (Gutierrez et al. 1999; Lindahl et al. 2001). Thus TGF-β could connect mechanical loading to type I collagen synthesis in tendinous tissue in vivo. The aim of the present study was to investigate whether exercise increases TGF-β levels both locally, in mechanically loaded tendon, and systemically (plasma).
The six male volunteers, who were included in the study (approved by the Ethical Committee of Copenhagen, KF) 11-088/01)) performed 1 h of uphill (3 %) treadmill running. Before and at several time points after exercise, levels of TGF-β were measured in plasma, and in the peritendinous tissue of the Achilles tendon by the microdialysis method (as described by Langberg et al. 1999). Before insertion of microdialysis catheters, an appropriate area of the skin was anaesthetised with lidocaine. Likewise, peritendon tissue levels of pro-collagen I C-terminal pro-peptide (PICP) and C-terminal telopeptide of type I collagen (ICTP), which indicate synthesis and breakdown of type I collagen, respectively, were measured to evaluate the local turnover of type I collagen.
After exercise, a rise in tissue levels of PICP was seen at 68 h post-exercise (from 0 µg l-1 to 52 ± 12.6 µg l-1; P < 0.05 vs. pre) (Wilcoxon signed ranks test). Tissue levels of TGF-β were 30 % higher 3 h post- vs. pre-exercise (423 ± 86 pg ml-1 post-exercise vs. 303 ± 46 pg ml-1 at rest) without reaching significance (n.s.) and also plasma concentrations of TGF-β rose 30 % in response to exercise (from 992 ± 49 pg ml-1 to 1301 ± 39 pg ml-1; P < 0.05 vs. pre) (Wilcoxon signed ranks test).
The changes seen after acute exercise are consistent with increased local synthesis of type I collagen in human peritendinous tissue. Although not conclusive, changes in circulating and local (though insignificant) TGF-β demonstrate a release of this cytokine in response to mechanical loading in vivo, and the time pattern is suggestive for a role of TGF-β in regulation of local collagen type I synthesis in tendon-related connective tissue subjected to mechanical loading.