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Proper mechanical stimulation can improve rotator cuff enthesis injury repair. However, the underlying mechanism of mechanical stimulation promoting injury repair is still unknown. In this study, we found that  Prrx1  +  cell was essential for murine rotator cuff enthesis development identified by single-cell RNA sequence and involved in the injury repair. Proper mechanical stimulation could promote the migration of  Prrx1  +  cells to enhance enthesis injury repair. Meantime, TGF-β signaling and primary cilia played an essential role in mediating mechanical stimulation signaling transmission. Proper mechanical stimulation enhanced the release of active TGF-β1 to promote migration of  Prrx1  +  cells. Inhibition of TGF-β signaling eliminated the stimulatory effect of mechanical stimulation on  Prrx1  +  cell migration and enthesis injury repair. In addition, knockdown of  Pallidin  to inhibit TGF-βR2 translocation to the primary cilia or deletion of  Ift88  in  Prrx1  +  cells also restrained the mechanics-induced  Prrx1  +  cells migration. These findings suggested that mechanical stimulation could increase the release of active TGF-β1 and enhance the mobilization of  Prrx1  +  cells to promote enthesis injury repair via ciliary TGF-β signaling.

Mechanical stimulation promotes enthesis injury repair by mobilizing Prrx1 + cells via ciliary TGF-β signaling