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

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-beta signaling and primary cilia played an essential role in mediating mechanical stimulation signaling transmission. Proper mechanical stimulation enhanced the release of active TGF-beta 1 to promote migration of Prrx1(+) cells. Inhibition of TGF-beta signaling eliminated the stimulatory effect of mechanical stimulation on Prrx1(+) cell migration and enthesis injury repair. In addition, knockdown of Pallidin to inhibit TGF-beta R2 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-beta 1 and enhance the mobilization of Prrx1(+) cells to promote enthesis injury repair via ciliary TGF-beta signaling.

Automated summary

Proper mechanical stimulation enhances the migration of Prrx1(+) cells and the release of active TGF-beta 1, promoting the repair of rotator cuff enthesis injuries through ciliary TGF-beta signaling.