Functional ?-adrenoceptors are important for early muscle regeneration in mice through effects on myoblast proliferation and differentiation.

ABSTRACT: 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 ?2-adrenoceptors (?-ARs) using ?2-AR agonists (?2-agonists) has been demonstrated previously, the exact role ?-ARs play in regulating the regenerative process remains unclear. To investigate ?-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 ?1-AR (?1-KO) and/or ?2-ARs (?2-KO), testing the hypothesis that muscles from mice lacking the ?2-AR would exhibit impaired functional regeneration after damage compared with muscles from ?1-KO or ?1/?2-AR null (?1/?2-KO) KO mice. At 7 days post-injury, regenerating muscles from ?1/?2-KO mice produced less force than those of controls but muscles from ?1-KO or ?2-KO mice did not exhibit any delay in functional restoration. Compared with controls, ?1/?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 ?-AR signaling pathway was unexpected and may have important implications for manipulating ?-AR signaling to improve the rate, extent and efficacy of muscle regeneration to enhance functional recovery after injury.

SUBMITTER: Church JE 

PROVIDER: S-EPMC4084885 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature