A CD26+ tendon stem progenitor cell population contributes to tendon repair and heterotopic ossification
Inadequate tendon healing and heterotopic bone formation result in substantial pain and disability, yet the specific cells responsible for tendon healing remain uncertain. Here we identify a CD26<sup>+</sup> tendon stem/progenitor cells residing in peritendon, which constitutes a primitive stem cell population with self-renewal and multipotent differentiation potentials. CD26<sup>+</sup> tendon stem/progenitor cells migrate into the tendon midsubstance and differentiation into tenocytes during tendon healing, while ablation of these cells led to insufficient tendon healing. Additionally, CD26<sup>+</sup> tendon stem/progenitor cells contribute to heterotopic ossification and Tenascin-C-Hippo signaling is involved in this process. Targeting Tenascin-C significantly suppresses chondrogenesis of CD26<sup>+</sup> tendon stem/progenitor cells and subsequent heterotopic ossification. Our findings provide insights into the identification of tendon stem/progenitor cells and illustrate the essential role of CD26<sup>+</sup> tendon stem/progenitor cells in tendon healing and heterotopic bone formation.
Authors
- Sifang Li (ORCID: https://orcid.org/0000-0002-9767-9640)
- Wenjun Hao (ORCID: https://orcid.org/0000-0002-9854-035X)
- Yingxin Lin (ORCID: https://orcid.org/0000-0002-4299-7326)
- Zemin Li (ORCID: https://orcid.org/0000-0002-7878-6870)
- Siwen Chen (ORCID: https://orcid.org/0000-0003-2138-7737)
- Jianru Wang (ORCID: https://orcid.org/0000-0002-9747-0652)
- Dongying Chen (ORCID: https://orcid.org/0000-0002-8934-7937)
- Hao Yang (ORCID: https://orcid.org/0000-0002-3505-9403)
- Shuai Zhang (ORCID: https://orcid.org/0000-0002-0648-921X)
- Xiang Li (ORCID: https://orcid.org/0000-0002-6849-353X)
- Zihao Li (ORCID: https://orcid.org/0009-0003-4082-5859)
- Hui Liu (ORCID: https://orcid.org/0000-0003-0754-402X)
- Hua Chao
- Zhongping Zhan (ORCID: https://orcid.org/0000-0003-1104-3826)
- Jingyu Zhang (ORCID: https://orcid.org/0009-0000-2921-0042)
Institutions
- The University of Sydney (AU)
- Sun Yat-sen University (CN)
- Peking University (CN)
- Beijing Jishuitan Hospital (CN)
- Key Laboratory of Guangdong Province (CN)
- The First Affiliated Hospital, Sun Yat-sen University (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-01-16
- DOI
- https://doi.org/10.1038/s41467-025-56112-5
- Citations
- 21
- Primary Topic
- Heterotopic Ossification and Related Conditions
- Type
- article
- Field-Weighted Citation Impact
- 35.03
Funders
- National Natural Science Foundation of China
- Sun Yat-sen University
- Guangdong Science and Technology Department
- National Postdoctoral Program for Innovative Talents
- National Key Research and Development Program of China