Involvement of collagen-inducing growth factors Ph.D. thesis

Acute exercise induces collagensynthesis in both tendon and muscle. Thisindicates an adaptive response in the connectivetissue of the muscle-tendon unit. However, it isnot known if regulation of collagen expression isdependent on the type of contraction performedby the muscle. Furthermore, the possibleinvolvement of collagen inducing growthfactors, such as transforming growth factor-β-1(TGF-β-1) and connective tissue growth factor(CTGF), in muscle/tendon adaptation has notbeen investigated. Female Sprague-Dawley ratswere subjected to 4 days of concentric-,eccentricor isometric training (n=7-9 pergroup) of the medial gastrocnemius, bystimulation of the sciatic nerve during generalanaesthesia. RNA was extracted from medialgastrocnemiusand Achilles tendon tissue 24 hafter the last training bout, and mRNA levels forcollagens I and -III, TGF-β-1 and CTGF weremeasured by Northern blotting and/or Real-timeRT PCR. In tendon, expression of TGF-β-1 andcollagens I and III (but not CTGF) increased inresponse to all types of training and nodifference was seen between contraction types.In muscle, TGF-β-1 mRNA increased in alltraining groups, but the effect of eccentrictraining was significantly greater thanconcentric. Furthermore, collagen I and CTGFexpression was induced in muscle by eccentric-and isometric training, but not by concentrictraining. In conclusion the study supports aninvolvement of TGF-β-1 in loading inducedcollagen synthesis in the muscle-tendon unit andimportantly, it indicates that muscle tissue ismore sensitive than tendon to the specificmechanical stimulus.INTRODUCTIONTendon tissue and the extracellular matrix(ECM) of skeletal muscle are collagen richtissues that are important for musclefunction, especially in relation to forcetransmission. The fibrillar collagens, type Iand -III, are the major components of tendonand muscle ECM. In tendon, type I collagenis predominant, while both types areexpressed at equal levels in muscle ECM(36). In cases of training leading to musclehypertrophy and increased strength, it seemsimperative that these collagen rich tissuesadapt in order to sustain the integrity of themuscle-tendon unit (27). In vivo humanstudies indicate that collagen synthesisincreases in both muscle and tendon inresponse to acute exercise (21; 30; 40; 41),and similarly prolonged training appears toelevate type I collagen synthesis in humantendon (29). These findings indicate thatcollagen synthesis, and possibly collagenmRNA expression, in tendon and muscle isregulated by exercise/training, and a fewstudies have in fact shown elevatedexpression levels of type I and III collagenmRNA in both muscle and tendon inresponse to loading in animals (2; 19; 28;47). Meanwhile, the knowledge on howspecific contraction types (e.g. concentricvs. eccentric) may influence collagenexpression and synthesis in a differentialmanner is very limited. In the present studywe have measured changes in tendonandmuscle expression of type I and III collagenin response to short-term training involving