1. Stem Cells and Regenerative Medicine

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

  1. Han Xiao
  2. Tao Zhang
  3. Chang Jun Li
  4. Yong Cao
  5. Lin Feng Wang
  6. Hua Bin Chen
  7. Sheng Can Li
  8. Chang Biao Guan
  9. Jian Zhong Hu
  10. Di Chen
  11. Can Chen  Is a corresponding author
  12. Hong Bin Lu  Is a corresponding author
  1. Xiangya Hospital Central South University, China
  2. Chinese Academy of Sciences, China
https://doi.org/10.7554/eLife.73614
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Cite this article
  1. Han Xiao
  2. Tao Zhang
  3. Chang Jun Li
  4. Yong Cao
  5. Lin Feng Wang
  6. Hua Bin Chen
  7. Sheng Can Li
  8. Chang Biao Guan
  9. Jian Zhong Hu
  10. Di Chen
  11. Can Chen
  12. Hong Bin Lu
(2022)
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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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

  1. Han Xiao

    Department of Sports Medicine, Xiangya Hospital Central South University, Changsha, China
    Competing interests
    The authors declare that no competing interests exist.

  2. Tao Zhang

    Department of Sports Medicine, Xiangya Hospital Central South University, Changsha, China
    Competing interests
    The authors declare that no competing interests exist.

  3. Chang Jun Li

    Department of Endocrinology, Xiangya Hospital Central South University, Changsha, China
    Competing interests
    The authors declare that no competing interests exist.

  4. Yong Cao

    Department of Spine Surgery, Xiangya Hospital Central South University, Changsha, China
    Competing interests
    The authors declare that no competing interests exist.

  5. Lin Feng Wang

    Department of Sports Medicine, Xiangya Hospital Central South University, Changsha, China
    Competing interests
    The authors declare that no competing interests exist.

  6. Hua Bin Chen

    Department of Sports Medicine, Xiangya Hospital Central South University, Changsha, China
    Competing interests
    The authors declare that no competing interests exist.

  7. Sheng Can Li

    Department of Sports Medicine, Xiangya Hospital Central South University, Changsha, China
    Competing interests
    The authors declare that no competing interests exist.

  8. Chang Biao Guan

    Department of Sports Medicine, Xiangya Hospital Central South University, Changsha, China
    Competing interests
    The authors declare that no competing interests exist.

  9. Jian Zhong Hu

    Department of Spine Surgery, Xiangya Hospital Central South University, Changsha, China
    Competing interests
    The authors declare that no competing interests exist.

  10. Di Chen

    Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
    Competing interests
    The authors declare that no competing interests exist.

  11. Can Chen

    Department of Orthopedic, Xiangya Hospital Central South University, Changsha, China
    For correspondence
    chencan@csu.edu.cn
    Competing interests
    The authors declare that no competing interests exist.

  12. Hong Bin Lu

    Department of Sports Medicine, Xiangya Hospital Central South University, Changsha, China
    For correspondence
    hongbinlu@hotmail.com
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7749-3593

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.

Reviewing Editor

  1. Fayez Safadi, Northeast Ohio Medical University, United States

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.

Version history

  1. Received: September 5, 2021
  2. Preprint posted: September 22, 2021 (view preprint)
  3. Accepted: April 26, 2022
  4. Accepted Manuscript published: April 27, 2022 (version 1)
  5. Version of Record published: May 11, 2022 (version 2)

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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  1. Han Xiao
  2. Tao Zhang
  3. Chang Jun Li
  4. Yong Cao
  5. Lin Feng Wang
  6. Hua Bin Chen
  7. Sheng Can Li
  8. Chang Biao Guan
  9. Jian Zhong Hu
  10. Di Chen
  11. Can Chen
  12. Hong Bin Lu
(2022)
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

Share this article

https://doi.org/10.7554/eLife.73614

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