Twisting paths: the paradox of fiber branching in muscle regeneration

Muscle regeneration following injury reveals a striking paradox: the same phenomenon, fiber branching, can serve as both a beneficial adaptation in healthy muscle and a pathological hallmark in disease. In healthy muscle, branched fibers emerge as an adaptive response to extreme mechanical loading, redistributing stress, enhancing hypertrophy, and protecting against injury. Conversely, in conditions such as Duchenne Muscular Dystrophy, excessive and complex branching contributes to mechanical weakness, increased susceptibility to damage, and progressive functional decline. This review explores the dichotomy of fiber branching in muscle physiology, synthesizing current research on its molecular and cellular mechanisms. By understanding the paradoxical nature of fiber branching, we aim to uncover new perspectives for therapeutic strategies that balance its adaptive and pathological roles to improve outcomes for muscle diseases.