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

Han Xiao; Tao Zhang; Changjun Li; Yong Cao; Linfeng Wang; Huabin Chen; Shengcan Li; Changbiao Guan; Jianzhong Hu; Di Chen; Can Chen; Hongbin Lu

doi:10.7554/eLife.73614

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

Elife. 2022 Apr 27:11:e73614. doi: 10.7554/eLife.73614.

Authors

Han Xiao^{1

2

3

4

5}, Tao Zhang^{1

2

3

4

6}, Changjun Li^{6

7}, Yong Cao^{2

3

4

6

8}, Linfeng Wang^{1

2

3

4

6}, Huabin Chen^{1

2

3

4

6}, Shengcan Li^{1

2

3

4

6}, Changbiao Guan^{1

2

3

4

6}, Jianzhong Hu^{2

3

4

6

8}, Di Chen⁹, Can Chen^{2

3

4

6

10}, Hongbin Lu^{1

2

3

4

6}

Affiliations

¹ Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, China.
² Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, China.
³ Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, Changsha, China.
⁴ Hunan Engineering Research Center of Sport and Health, Changsha, China.
⁵ Department of pediatric orthopedic, Hunan Children's hospital, Changsha, China.
⁶ National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
⁷ Department of Endocrinology, Xiangya Hospital, Central South University, Changsha, China.
⁸ Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha, China.
⁹ Faculty of Pharmaceutical Sciences, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
¹⁰ Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, 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.

Keywords: Prx1+ cells; TGF-β; enthesis; mechanical stimulation; mouse; primary cilia; regenerative medicine; stem cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Mice
Rotator Cuff / metabolism
Rotator Cuff Injuries* / genetics
Transforming Growth Factor beta1* / metabolism

Substances

Transforming Growth Factor beta1

Grants and funding

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.