transforming-growth-factor-beta and Sprains-and-Strains

Muscle strain injuries are extremely common in sports medicine. Muscle healing often is hindered by scar tissue formation after injury.. Suramin can prevent scar tissue formation and improve muscle healing after injury because of its ability to antagonize transforming growth factor-beta1, a fibrotic cytokine.. Controlled laboratory study.. In vitro, muscle-derived fibroblasts (a potential cell source of muscle fibrosis) were incubated with suramin and/or transforming growth factor-beta1; a cell growth curve was obtained. In vivo, mouse gastrocnemius muscles were strain injured. Suramin or sham/control intramuscular injections were performed after injury at various time points. Mice were sacrificed at various time points after injury, and skeletal muscle tissue was evaluated by using histological and physiological tests. Statistical analysis was performed by using analysis of variance and Fisher tests.. Suramin decreased the stimulating effect of transforming growth factor-beta1 on the growth of muscle-derived fibroblasts in vitro. Significantly less fibrous scar formation was observed in suramin-treated muscles than in sham-injected muscles. The fast-twitch and tetanus strength of suramin-treated muscles was also significantly greater relative to that of control muscles.. Suramin blocked the stimulatory effect of transforming growth factor-beta1 on muscle-derived fibroblasts in vitro. Suramin also reduced fibrous scar formation in muscle and enhanced muscle strength in strain-injured skeletal muscle.. These results may facilitate the development of strategies to enhance muscle healing after injury.

Topics: Animals; Antineoplastic Agents; Cicatrix; Fibroblasts; Mice; Mice, Inbred C57BL; Muscle, Skeletal; Sprains and Strains; Suramin; Transforming Growth Factor beta; Wound Healing

Muscle strains, frequently the result of a lengthening contraction, sometimes are treated with corticosteroids. We tested whether an injection of dexamethasone administered soon after muscle injury would minimize inflammation and facilitate the recovery of contractile tension. We applied one eccentric contraction on the tibialis anterior of 76 rats, which were randomly assigned to one of three groups: sham-injured plus dexamethasone, injured plus vehicle, and injured plus dexamethasone. Electrophysiology, histology, and reverse transcription-polymerase chain reaction were used to study the relation between contractile tension, inflammation, and the expression of inflammatory molecules. The single eccentric contraction led to a reversible muscle injury characterized initially by reduced contractile tension and inflammation. The dexamethasone injection reduced the expression of interleukin-1beta and transforming growth factor-beta1 compared with injured vehicle-injected controls and led to a transient improvement of contractile tension 3 days after the injury. No adverse effects were seen for as much as 3 weeks after the dexamethasone injection. The data indicate that one dose of dexamethasone administered soon after muscle strain may facilitate recovery of contractile tension without causing major adverse consequences in this experimental model.

Topics: Animals; Anti-Inflammatory Agents; Biomarkers; Dexamethasone; Interleukin-1; Male; Muscle Contraction; Muscle, Skeletal; Myositis; Rats; Rats, Sprague-Dawley; Recovery of Function; Sprains and Strains; Transforming Growth Factor beta; Transforming Growth Factor beta1

The application of mechanical strain leads to activation of human brain natriuretic peptide gene promoter activity, a marker of hypertrophy, in cultured neonatal rat ventricular myocytes. We have used a combination of transient transfection analysis and reverse transcriptase-polymerase chain reaction to examine the role of locally produced factors in contributing to this activation. Conditioned media from strained, but not static, cultures led to a dose-dependent increase in human brain natriuretic peptide gene promoter activity. This increase was completely blocked by losartan or BQ-123, implying a role for angiotensin and endothelin as autocrine/paracrine mediators of the response to strain. Inclusion of the same antagonists in the cultures themselves led to only partial inhibition (approximately 60%), whereas inclusion of exogenous endothelin or angiotensin II resulted in amplification of the strain response. Angiotensin II and endothelin appear to be arrayed in series in the regulatory circuitry; the angiotensin response was blocked by BQ-123, whereas the endothelin response was unaffected by losartan. Mechanical strain was also shown to stimulate expression of the endogenous angiotensinogen, angiotensin-converting enzyme, and endothelin genes in this system. Collectively, these data indicate that locally generated angiotensin II and endothelin, acting in series, play an important autocrine/paracrine role in mediating strain-dependent activation of cardiac-specific gene expression.

Topics: Angiotensin II; Animals; Antibodies; Autocrine Communication; Cells, Cultured; Culture Media, Conditioned; Endothelin-1; Gene Expression Regulation; Genes, Reporter; Humans; Losartan; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Paracrine Communication; Peptides, Cyclic; Promoter Regions, Genetic; Rats; RNA, Messenger; Sprains and Strains; Transfection; Transforming Growth Factor beta; Ventricular Function