Connective tissue regeneration in skeletal muscle after eccentric contraction-induced injury

Human skeletal muscle has the potential to regenerate completely after injury induced under controlled experimental conditions. The events inside the myofibres as they undergo necrosis, followed closely by satellite cell mediated myogenesis, have been mapped in detail. Much less is known about the adaptation throughout this process of both the connective tissue structures surrounding the myofibres, and the fibroblasts, the cells responsible for synthesising this connective tissue. However, the few studies investigating muscle connective tissue remodelling demonstrate a strong response that appears to be sustained for a long time after the major myofibre responses have subsided. While the use of electrical stimulation to induce eccentric contractions versus voluntary eccentric contractions appears to lead to a greater extent of myofibre necrosis and regenerative response, this difference is not apparent when the muscle connective tissue responses are compared, although further work is required to confirm this. Pharmacological agents (growth hormone and angiotensin II type I receptor blockers) are considered in the context of accelerating the muscle connective tissue adaptation to loading. Cautioning against this however is the association between muscle matrix protein remodelling and protection against re-injury, which suggests that a (so far undefined) period of vulnerability to re-injury may exist during the remodelling phases. The role of individual muscle matrix components and their spatial interaction during adaptation to eccentric contractions is an unexplored field in human skeletal muscle and may provide insight into the optimal timing of rest vs. return to activity after muscle injury.

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