2. Academic Validation
  3. Procr+ chondroprogenitors sense mechanical stimuli to govern articular cartilage maintenance and regeneration

Procr+ chondroprogenitors sense mechanical stimuli to govern articular cartilage maintenance and regeneration

  • Cell. 2025 Jul 21:S0092-8674(25)00738-X. doi: 10.1016/j.cell.2025.06.036.
Qiaoling Zhu 1,  Feng Yin 2,  Jiachen Qin 1,  Wanyu Shi 1,  Yaojia Liu 1,  Yuanyuan Zhao 1,  Jianfang Wang 1,  Lei Zhang 3,  Aoyuan Fan 2,  Dandan Cao 1,  Qiqi Peng 1,  Bin Zhou 4,  Lijun Wang 5,  Weiguo Zou 6,  Rui Yue 7
Affiliations

Affiliations

  • 1 State Key Laboratory of Cardiovascular Diseases and Medical Innovation Center, Shanghai East Hospital, Frontier Science Center for Stem Cell Research, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
  • 2 Department of Joint Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200092, China.
  • 3 Shanghai Engineering Research Center of Tooth Restoration and Regeneration & Tongji Research Institute of Stomatology & Department of Implantology, Shanghai Tongji Stomatological Hospital and Dental School, Tongji University, Shanghai 200072, China.
  • 4 New Cornerstone Science Laboratory, Key Laboratory of Multi-cell Systems, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.
  • 5 Hainan Institute of Regenerative Orthopedics and Sports Medicine, Hainan Academy of Medical Sciences and School of Basic Medicine, Hainan Medical University, 570000 Hainan, China; Key Laboratory of RNA Innovation, Science and Engineering, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.
  • 6 Hainan Institute of Regenerative Orthopedics and Sports Medicine, Hainan Academy of Medical Sciences and School of Basic Medicine, Hainan Medical University, 570000 Hainan, China; Key Laboratory of RNA Innovation, Science and Engineering, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China. Electronic address: zouwg94@sibcb.ac.cn.
  • 7 State Key Laboratory of Cardiovascular Diseases and Medical Innovation Center, Shanghai East Hospital, Frontier Science Center for Stem Cell Research, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China; Shanghai Institute of Stem Cell Research and Clinical Translation, Shanghai 200120, China. Electronic address: ryue@tongji.edu.cn.
PMID: 40695281 DOI: 10.1016/j.cell.2025.06.036
Abstract

Protein C receptor+ (Procr+) cells were identified as stem or progenitor cells in multiple adult tissues. However, whether mechanical stimuli fine-tune their activation and differentiation remain unknown. Here, we found rare Procr+ cells in the superficial layer of tibial articular cartilage and meniscus, which keep replenishing chondrocytes in postnatal knee joints. Mechanical stimulation by forced running significantly increased the frequency of Procr+ cells, whereas mechanical unloading by tail suspension showed opposite effects. Osteoarthritis (OA) activated Procr+ cells to repair cartilage erosion, whereas genetic ablation of Procr+ cells accelerated OA progression. Pharmacological or genetic inhibition of the mechanosensor Piezo1 significantly blunted cartilage regeneration by Procr+ cells and exacerbated OA. In contrast, intra-articular administration of a Piezo1 agonist ameliorated OA symptoms. Purified mouse or human Procr+ superficial cells robustly repair articular cartilage after expansion and in vivo transplantation. Together, we discovered a mechanosensitive chondroprogenitor population indispensable for articular cartilage maintenance and regeneration.

Keywords

chondroprogenitor; mechanical stimulation; osteoarthritis; procr; regeneration.

Figures
Products