PIEZO1 activation enhances myogenesis and mitigates muscle degeneration in rotator cuff tear.

Muscle degeneration is a common issue caused by rotator cuff tear (RCT) which significantly affects prognosis. Muscle stem cells (MuSCs) play a crucial role to prevent muscle degeneration after RCT. However, the pathological changes and detailed molecular mechanism underlying the myogenesis of MuSCs after RCT remain incomplete. The current study established single-cell landscape of supraspinatus muscles and found decreased expression of PIEZO1 and impaired myogenic potential of MuSCs from RCT patients. Reduced expression of PIEZO1 impaired the myogenesis of MuSCs by inhibiting the ERK/MAPK pathways. Furthermore, selective PIEZO1 agonist Yoda1 had the potential to alleviate muscle degeneration and improve shoulder function following RCT. This study emphasized the role of PIEZO1 in the myogenesis of MuSCs and suggested that activating PIEZO1 could be a potential non-surgical treatment option to reduce muscle degeneration after RCT.