2. Academic Validation
  3. GLP-1 receptor agonist liraglutide facilitates rotator cuff healing by reducing tendon cell inflammation and endoplasmic reticulum stress through the GLP-1R-AMPK/SIRT1 pathway

GLP-1 receptor agonist liraglutide facilitates rotator cuff healing by reducing tendon cell inflammation and endoplasmic reticulum stress through the GLP-1R-AMPK/SIRT1 pathway

  • Int Immunopharmacol. 2026 Jan 15:169:116010. doi: 10.1016/j.intimp.2025.116010.
Xiong Zhang 1,  Ruimin Chi 2,  Jingting Xu 3,  Chen Meng 3,  Zhenggang Wang 3,  Wanjun Ruo 4,  Fei Xin 3,  Tao Xu 5,  Fengjing Guo 6,  Genchun Wang 7,  Yaping Ye 8
Affiliations

Affiliations

  • 1 Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China. Electronic address: [email protected].
  • 2 Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095#, Jie-Fang Avenue, Qiaokou District, Wuhan 430030, Hubei, China; Institute of Drug Innovation, School of Medicine and Pharmaceutical Engineering, Taizhou Vocational and Technical College, Taizhou, China.
  • 3 Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
  • 4 Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 5 Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095#, Jie-Fang Avenue, Qiaokou District, Wuhan 430030, Hubei, China. Electronic address: [email protected].
  • 6 Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China. Electronic address: [email protected].
  • 7 Orthopedic Medical Center, Union Hospital, Fujian Medical University, Fuzhou, Fujian 350000, China. Electronic address: [email protected].
  • 8 Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China. Electronic address: [email protected].
PMID: 41386184 DOI: 10.1016/j.intimp.2025.116010
Abstract

Rotator cuff injuries are a common cause of shoulder pain with limited treatment options. Recent studies highlight inflammation's role in tendinopathy. GLP-1R agonists have shown anti-inflammatory effects in various diseases, but their role in rotator cuff injuries is unclear. This study investigates Liraglutide's (LIRA) effects on tendon cell inflammation, Apoptosis, and endoplasmic reticulum stress in vitro and its therapeutic effects on rat rotator cuff repair in vivo. LIRA significantly inhibits IL-1β-induced inflammation, enhances tendon cell anabolism, and upregulates the AMPK/SIRT1 pathway. Mechanistically, GLP-1R interacts with SIRT1 to prevent tendon cell Apoptosis and endoplasmic reticulum stress. LIRA effectively promotes tissue regeneration and restores biomechanical strength in a rat rotator cuff injury model. These findings suggest LIRA's therapeutic potential for rotator cuff repair and highlight GLP-1R activation as a key mechanism.

Keywords

Apoptosis; ER stress; GLP-1R; Rotator cuff injury; SIRT1.

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