2. Academic Validation
  3. Fibrous-layer resident Angptl7+ periosteal stem cells sense injury inflammation to orchestrate fracture repair

Fibrous-layer resident Angptl7+ periosteal stem cells sense injury inflammation to orchestrate fracture repair

  • Cell Res. 2026 Feb;36(2):121-136. doi: 10.1038/s41422-025-01202-8.
Bo Jiang # 1 2,  Wenhui Xing # 2,  Xiaocui Xu # 3,  Shuqin Chen # 2,  Heng Feng 1,  Rui Shao 4,  Jiatong Sun 3,  Yazhuo Zhang 1,  Zaiqi Xie 1,  Wenxiang Wang 1,  Xubin Yin 1,  Yi Wang 1,  Miaomiao Wang 1,  Ling Li 1,  Zhong Zhang 2,  Bo Gao 5,  Jinlong Suo 4,  Xuye Hu 1,  Lijun Wang 2,  Jun Sun 6,  Bin Zhou 7,  Bo O Zhou 7,  Matthew B Greenblatt 8 9,  Rongrong Le 10,  Weiguo Zou 11 12
Affiliations

Affiliations

  • 1 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, China.
  • 2 Key Laboratory of Emergency and Trauma of Ministry of Education, Hainan Academy of Medical Sciences, Hainan Medical University, Haikou, Hainan, China.
  • 3 Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
  • 4 Shanghai Institute of Microsurgery on Extremities, and Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
  • 5 Institute of Orthopaedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
  • 6 Key Laboratory of Immune Response and Immunotherapy, School of Basic Medical Sciences, University of Science and Technology of China, Hefei, Anhui, China.
  • 7 Key Laboratory of Multi-Cell Systems, 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, China.
  • 8 Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.
  • 9 Research Division, Hospital for Special Surgery, New York, NY, USA.
  • 10 Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China. [email protected].
  • 11 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, China. [email protected].
  • 12 Key Laboratory of Emergency and Trauma of Ministry of Education, Hainan Academy of Medical Sciences, Hainan Medical University, Haikou, Hainan, China. [email protected].
  • # Contributed equally.
PMID: 41501190 DOI: 10.1038/s41422-025-01202-8
Abstract

Periosteum contains abundant Ctsk-lineage skeletal stem cells (P-SSCs) that are key drivers of intramembranous ossification during bone development and maintenance. However, P-SSCs regenerate fractured bones by mediating endochondral ossification, raising the question of whether distinct P-SSCs subsets separately mediate steady-state bone formation and fracture repair. Here we uncover the heterogeneity of P-SSCs, identifying an Angptl7-expressing quiescent P-SSCs subset, which is restricted to the fibrous-layer of periosteum and barely contributes to postnatal bone development. After bone fracture, these cells largely contribute to bone healing by dedicating to endochondral ossification, regenerating the entire bone architecture. Dysfunction of Angptl7-lineage P-SSCs strongly impairs the bone healing process but does not affect steady-state bone formation. Multimodal analysis reveals that these cells can be immediately activated under the regulation of TNF-α/NF-κB signaling, subsequently acquiring osteogenic capacity. Together, our findings unravel an injury-specified P-SSCs subpopulation, providing a model that there are tissue-resident stem cells specialized for injury repair, while parallel stem cells maintain homeostasis.

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