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

Autor: Han Xiao, Tao Zhang, Changjun Li, Yong Cao, Linfeng Wang, Huabin Chen, Shengcan Li, Changbiao Guan, Jianzhong Hu, Di Chen, Can Chen, Hongbin Lu
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: eLife, Vol 11 (2022)
Druh dokumentu: article
ISSN: 2050-084X
DOI: 10.7554/eLife.73614
Popis: 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.
Databáze: Directory of Open Access Journals