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  3. Single cell atlas decodes the molecular dynamics of scar repair after human rotator cuff tear

Single cell atlas decodes the molecular dynamics of scar repair after human rotator cuff tear

  • Bone Res. 2026 Feb 5;14(1):17. doi: 10.1038/s41413-025-00501-5.
Yiming Qin # 1 2 3 4 5,  Guang Yang # 1 3 5 6,  Tao Zhang 1 3 5 7,  Yuying Yang 1 3 5 7,  Liyang Wan 1 3 5 7,  Tao Zhang 1 3 5 7,  Linfeng Wang 3 5 7 8,  Zhiyu Hu 1 3 7,  Zhu Dai 8,  Hongkang Zhou 9,  Chengjun Li 1 3 5 7,  Jianzhong Hu 10 11 12 13,  Hongbin Lu 14 15 16 17
Affiliations

Affiliations

  • 1 Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, China.
  • 2 Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, China.
  • 3 Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, China.
  • 4 Mobile Health Ministry of Education, China Mobile Joint Laboratory, Changsha, China.
  • 5 National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
  • 6 Department of Rehabilitation Medicine, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.
  • 7 Hunan Engineering Research Center of Sports and Health, Changsha, China.
  • 8 Department of Orthopedics, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China.
  • 9 Institute for Advanced Study, Central South University, Changsha, China.
  • 10 Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, China. [email protected].
  • 11 Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, China. [email protected].
  • 12 Mobile Health Ministry of Education, China Mobile Joint Laboratory, Changsha, China. [email protected].
  • 13 National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China. [email protected].
  • 14 Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, China. [email protected].
  • 15 Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, China. [email protected].
  • 16 National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China. [email protected].
  • 17 Hunan Engineering Research Center of Sports and Health, Changsha, China. [email protected].
  • # Contributed equally.
PMID: 41644521 DOI: 10.1038/s41413-025-00501-5
Abstract

Irreversible fibrotic scarring after rotator cuff tear (RCT) compromises the mechanical properties of the healing tendon, yet the underlying mechanisms remain poorly understood. Here, we analyzed the histological features of human RCT scars, characterized by disruption of tendon architecture, disorganized Collagen fibrils, and imbalance in type I/III Collagen ratios and fibril diameters. Using single-cell RNA Sequencing of tendon stumps from patients with RCT, we deconvolved the cellular and molecular landscape of the fibrotic scarring microenvironment. Heterogenous pro-fibrotic subclusters were identified and validated to participate into scar formation, including tendon stem cell, senescent tenocyte, SOX9-driven pro-fibrotic macrophage, and pro-fibrotic endothelial cells undergoing endothelial-mesenchymal transition (EndoMT). Furthermore, we found that Osteopontin and TGF-β signaling were key drivers of extracellular matrix deposition, and their blockade ameliorated fibrotic scarring after RCT. Collectively, our study dissected the dynamic scarring microenvironment in human RCT and highlights potential therapeutic targets for preventing pathological scar formation.

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