Beneficial effects of cannabinoid receptor type 2 (CB2R) in injured skeletal muscle post-contusion

Abstract

The aim of the current study was to investigate the effects of cannabinoid receptor type 2 (CB2R) on the repair process of injured skeletal muscle, which could potentially lay solid foundations as a novel target for curing muscular fibrosis in future. A standardized rat model of skeletal muscle contusion was established, where rats were treated with the CB2R agonist JWH-133 or antagonist AM-630. The in vivo results revealed that CB2R activation with JWH-133 significantly diminished the fibrotic areas, downregulated the mRNA levels of collagen type I/ІІІ and augmented the number of multinucleated regenerating myofibers in the injured zones. The reasons leading to the aforementioned results were directly attributable to decreased mRNA levels of TGF-β1, FN-EIIIA and αSMA, reduced accumulation of myofibroblasts, and concomitantly increased mRNA levels of matrix metalloproteinase-1/2. However, we observed contrasting changes in rats treated with the CB2R antagonist AM-630. These results revealed multiple effects of CB2R in systematically inhibiting fibrotic formation and improving muscle regeneration, alongside its potential for clinical application in patients with skeletal muscle injuries and diseases.