Mechanical stimulation promotes enthesis injury repair by mobilizing Prrx1+ cells via ciliary TGF-β signaling
- Xiangya Hospital Central South University, China
- Chinese Academy of Sciences, China
Abstract
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.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting file; Source Data files have been provided for Figures 1 and 2. Figure 3 - Source Data, Figure 4 - Source Data, Figure 5 - Source Data, Figure 6 - Source, Figure 7 - Source Data, Figure 8 - Source Data contain the numerical data used to generate the figures.
Article and author information
Author details
Funding
National Natural Science Foundation of China (No. 81730068)
- Hong Bin Lu
Major Science and technology progect of Changsha Science and Technology Bureau (No. 41965)
- Hong Bin Lu
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animal care protocols and experiments in this study were reviewed and approved by the Animal Care and Use Committees of the Laboratory Animal Research Center of our institute. All mice were maintained in the specific pathogen-free facility of the Laboratory Animal Research Center.
Copyright
© 2022, Xiao et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Mechanical stimulation promotes enthesis injury repair by mobilizing Prrx1+ cells via ciliary TGF-β signaling
eLife 11:e73614.
https://doi.org/10.7554/eLife.73614
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