2. Academic Validation
  3. Piezo1 balances the osteogenic-tenogenic plasticity of periosteal progenitor cells through the YAP pathway

Piezo1 balances the osteogenic-tenogenic plasticity of periosteal progenitor cells through the YAP pathway

  • Cell Rep. 2025 May 27;44(5):115630. doi: 10.1016/j.celrep.2025.115630.
Lijun Wang 1,  Qian Ren 2,  Shuqin Chen 3,  Lixiang Lou 2,  Xuye Hu 2,  Wenhui Xing 2,  Jinlong Suo 4,  Jun Sun 5,  Matthew B Greenblatt 5,  Heng Feng 2,  Weiguo Zou 6
Affiliations

Affiliations

  • 1 Hainan Institute of Regenerative Orthopedics and Sports Medicine, Hainan Academy of Medical Sciences and School of Basic Medicine, Hainan Medical University, Hainan 570000, China; Institute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China. Electronic address: hy0224010@hainmc.edu.cn.
  • 2 Key Laboratory of RNA Innovation, Science and Engineering, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
  • 3 Hainan Institute of Regenerative Orthopedics and Sports Medicine, Hainan Academy of Medical Sciences and School of Basic Medicine, Hainan Medical University, Hainan 570000, China.
  • 4 Institute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
  • 5 Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.
  • 6 Hainan Institute of Regenerative Orthopedics and Sports Medicine, Hainan Academy of Medical Sciences and School of Basic Medicine, Hainan Medical University, Hainan 570000, China; Key Laboratory of RNA Innovation, Science and Engineering, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China; Institute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China. Electronic address: zouwg94@sibcb.ac.cn.
PMID: 40286268 DOI: 10.1016/j.celrep.2025.115630
Abstract

The extremity tendons and bones are derived from limb bud mesenchyme, which eventually becomes cells of different tissues. Despite their common origin, it was widely believed that tenocytes and skeletal cells are distinct lineages without interconversion. However, we found that periosteal skeletal progenitor cells could transform between osteogenic and tenogenic commitment. SCX can label the periosteal progenitor cell population. Loss of Piezo1 arrests the periosteal progenitor cells in a progenitor state. Piezo1 deficiency leads to upregulation of Scx expression due to the inhibited YAP nuclear localization. Loss of Piezo1 showed increased tenogenic marker genes and decreased osteogenic marker genes. The periosteal progenitor cells can regenerate the injured tendon more robustly when Piezo1 is absent. Taken together, our data reveal that periosteal SCX+ progenitor cells compromise the osteogenic ability and acquire the tenocyte-biased lineage commitment after loss of Piezo1, providing a strategy to modulate the periosteal progenitor cells for tissue regeneration.

Keywords

CP: Cell biology; CP: Stem cell research; Piezo1; bone repair; lineage plasticity; periosteal progenitor cells; tendon repair.

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