Functional Beta-Adrenoceptors Are Important For Early Muscle Regeneration In Mice Through Effects On Myoblast Proliferation And Differentiation

Muscles can be injured in different ways and the trauma and subsequent loss of function and physical capacity can impact significantly on the lives of patients through physical impairments and compromised quality of life. The relative success of muscle repair after injury will largely determine the extent of functional recovery. Unfortunately, regenerative processes are often slow and incomplete, and so developing novel strategies to enhance muscle regeneration is important. While the capacity to enhance muscle repair by stimulating beta(2)-adrenoceptors (beta-ARs) using beta(2)-AR agonists (beta(2)-agonists) has been demonstrated previously, the exact role beta-ARs play in regulating the regenerative process remains unclear. To investigate beta-AR-mediated signaling in muscle regeneration after myotoxic damage, we examined the regenerative capacity of tibialis anterior and extensor digitorum longus muscles from mice lacking either beta(1)-AR (beta(1)-KO) and/or beta(2)-ARs (beta(2)-KO), testing the hypothesis that muscles from mice lacking the beta(2)-AR would exhibit impaired functional regeneration after damage compared with muscles from beta(1)-KO or beta(1)/b(2)-AR null (beta(1)/beta(2)-KO) KO mice. At 7 days post-injury, regenerating muscles from beta(1)/beta(2)-KO mice produced less force than those of controls but muscles from beta(1)-KO or beta(2)-KO mice did not exhibit any delay in functional restoration. Compared with controls, beta(1)/beta(2)-KO mice exhibited an enhanced inflammatory response to injury, which delayed early muscle regeneration, but an enhanced myoblast proliferation later during regeneration ensured a similar functional recovery (to controls) by 14 days post-injury. This apparent redundancy in the beta-AR signaling pathway was unexpected and may have important implications for manipulating beta-AR signaling to improve the rate, extent and efficacy of muscle regeneration to enhance functional recovery after injury.