Volume 36, No 2, Feb 2026

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 36 Issue 2, February 2026: 121-136   |  Open Access

ORIGINAL ARTICLES

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

Bo Jiang^1,2,† , Wenhui Xing^2,† , Xiaocui Xu^3,† , Shuqin Chen^2,† , Heng Feng¹ , Rui Shao⁴ , Jiatong Sun³ , Yazhuo Zhang¹ , Zaiqi Xie¹ , Wenxiang Wang¹ , Xubin Yin¹ , Yi Wang¹ , Miaomiao Wang¹ , Ling Li¹ , Zhong Zhang² , Bo Gao⁵ , Jinlong Suo⁴ , Xuye Hu¹ , Lijun Wang² , Jun Sun⁶ , Bin Zho⁷ , Bo O. Zhou⁷ , Matthew B. Greenblatt^8,9 , Rongrong Le^3,* , Weiguo Zou^1,2,*

¹Key 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
²Key Laboratory of Emergency and Trauma of Ministry of Education, Hainan Academy of Medical Sciences, Hainan Medical University, Haikou, Hainan, China
³Shanghai 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
⁴Shanghai Institute of Microsurgery on Extremities, and Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China
⁵Institute of Orthopaedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, China
⁶Key Laboratory of Immune Response and Immunotherapy, School of Basic Medical Sciences, University of Science and Technology of China, Hefei, Anhui, China
⁷Key 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
⁸Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA
⁹Research Division, Hospital for Special Surgery, New York, NY, USA
^†These authors contributed equally: Bo Jiang, Wenhui Xing, Xiaocui Xu, Shuqin Chen
Correspondence: Rongrong Le(lerongrong@tongji.edu.cn)Weiguo Zou(zouwg94@sibcb.ac.cn)

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.

https://doi.org/10.1038/s41422-025-01202-8

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