Leptin Enhances M1 Macrophage Polarization and Impairs Tendon-Bone Healing in Rotator Cuff Repair: A Rat Model

作者：Yinghao Li, Lei Yao, Yizhou Huang, Long Pang, Chunsen Zhang, Tao Li, Duan Wang, Kai Zhou, Jian Li, Xin Tang · 发表于：Clinical Orthopaedics and Related Research · 年份：2025 · DOI：10.1097/corr.0000000000003428 · 被引用次数：19 · 研究领域：Shoulder Injury and Treatment、Tendon Structure and Treatment、Nerve Injury and Rehabilitation

BACKGROUND: Rotator cuff tears are common, affecting more than 60% of individuals older than 80 years, and they have been implicated in 70% of patients with shoulder pain. M1 polarization-related inflammation has been reported to be associated with poor healing outcomes of rotator cuff injury, and leptin, an adipokine, has been reported to be a potential activator of inflammation. However, whether leptin affects rotator cuff repair remains unknown. QUESTIONS/PURPOSES: Using in vitro cell experiments and an in vivo rat rotator cuff tear model, we therefore asked: (1) Does leptin promote the M1 polarization of macrophages in vitro and in vivo? (2) Does leptin impair biomechanical strength, the histologic structure of the tendon-bone interface, bone mineral density (BMD), or gait in the rotator cuff tear scenario? (3) Does leptin promote M1 polarization by upregulating the tumor necrosis factor (TNF) pathway? METHODS: The impact of leptin on M1 macrophage polarization in vitro was determined by reverse transcription-polymerase chain reaction (RT-PCR), the Western blot test, and immunofluorescence staining. The effect of leptin on tendon-bone healing was assessed in an in vivo rat rotator cuff tear model by comparing a leptin group with a suture group in terms of gait, biomechanical tensile strength, the histologic structure of the tendon-bone interface, and BMD. In the in vivo experiments, 8-week-old male Sprague Dawley rats were used, adapting a previously developed rat rotator...