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.

中文翻译：

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机械刺激通过纤毛 TGF-β 信号传导动员 Prx1+ 细胞促进附着点损伤修复

适当的机械刺激可以改善肩袖附着点损伤的修复。然而，机械刺激促进损伤修复的潜在机制尚不清楚。在这项研究中，我们发现 Prx1 ⁺细胞对于通过单细胞 RNA 序列鉴定并参与损伤修复的鼠肩袖附着点发育至关重要。适当的机械刺激可以促进Prx1 ⁺细胞的迁移以增强附着点损伤的修复。同时，TGF-β 信号传导和初级纤毛在介导机械刺激信号传导中起重要作用。适当的机械刺激增强活性 TGF-β1 的释放以促进 Prx1 ^{+ 的}迁移细胞。抑制 TGF-β 信号消除了机械刺激对 Prx1 ⁺细胞迁移和附着点损伤修复的刺激作用。此外，敲除Pallidin抑制TGF-βR2易位至初级纤毛或缺失的IFT88中的Prx1 ⁺细胞还抑制了力学诱导的Prx1 ⁺细胞的迁移。这些发现表明机械刺激可以增加活性 TGF-β1 的释放并增强 Prx1 ⁺细胞的动员，以通过纤毛 TGF-β 信号传导促进附着点损伤修复。