Mechanical stimulation promotes enthesis injury repair by mobilizing Prx1⁺ cells via ciliary TGF-β signaling

Abstract

Proper mechanical stimulation can improve rotator cuff enthsis injury repair. However, the underlying mechanism of mechanical stimulation promoting injury repair is still unknown. In this study, we found that Prx1⁺ 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 Prx1⁺ 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 Prx1⁺ cells. Inhibition of TGF-β signaling eliminated the stimulatory effect of mechanical stimulation on Prx1⁺ 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 Prx1⁺ cells also restrained the mechanics-induced Prx1⁺ cells migration. These findings suggested that mechanical stimulation could increase the release of active TGF-β1 and enhance the mobilization of Prx1⁺ cells to promote enthesis injury repair via ciliary TGF-β signaling.