Department of Orthopaedics, Icahn School of Medicine at Mount Sinai, New York, New York.
Department of Orthopaedic Surgery and Traumatology, Inselspital, Bern University Hospital, University of Bern, Shoulder, Elbow and Orthopaedic Sports Medicine, Bern, Switzerland.
J Orthop Res. 2021 Aug;39(8):1789-1799. doi: 10.1002/jor.24769. Epub 2020 Jun 15.
Rotator cuff supraspinatus tendon injuries are common with high rates of anatomic failure after surgical repair. The purpose of the study was to define clinically relevant features of a mouse model of supraspinatus tendon injury to determine painful, functional, and structural outcomes; we further investigated two cell populations mediating healing using genetic lineage tracing after full detachment and repair of the supraspinatus tendon in mice. The pain was assessed using the mouse grimace scale and function by gait analysis and tensile testing. Histological and microCT analyses were used to determine enthesis/tendon and bone structure, respectively. Lineage tracing was carried out using inducible Cre lines for ScxCreERT2 (tendon cells) and αSMACreERT2 (myofibroblasts and mesenchymal progenitors). Mice only expressed pain transiently after surgery despite long-term impairment of functional and structural properties. Gait, tensile mechanical properties, and bone properties were significantly reduced after injury and repair. Lineage tracing showed relatively few Scx tendon cells while αSMA cells contributed strongly to scar formation. Despite surgical reattachment of healthy tendon, lineage tracing revealed poor preservation of supraspinatus tendon after acute injury and loss of tendon structure, suggesting that tendon degeneration is also a key impediment of successful rotator cuff repair. Scar formation after surgery is mediated largely by αSMA cells and results in permanently reduced functional and structural properties.
肩袖冈上肌腱损伤在外科修复后常出现解剖学失败，其发生率较高。本研究的目的是确定冈上肌腱损伤小鼠模型的临床相关特征，以确定疼痛、功能和结构结果；我们进一步研究了两种细胞群，在冈上肌腱完全分离和修复后，使用遗传谱系追踪来介导愈合。疼痛通过小鼠面部表情评分进行评估，功能通过步态分析和拉伸测试进行评估。组织学和 microCT 分析分别用于确定附著点/肌腱和骨骼结构。谱系追踪使用 ScxCreERT2（肌腱细胞）和αSMACreERT2（肌成纤维细胞和间充质祖细胞）的诱导型 Cre 线进行。尽管长期存在功能和结构损伤，但手术后小鼠仅表现出短暂的疼痛。步态、拉伸力学性能和骨骼特性在损伤和修复后均显著降低。谱系追踪显示 Scx 肌腱细胞相对较少，而αSMA 细胞强烈参与瘢痕形成。尽管健康肌腱进行了手术重新附着，但谱系追踪显示急性损伤后冈上肌腱的保存不佳，肌腱结构丢失，这表明肌腱退变也是成功修复肩袖的一个关键障碍。手术后的瘢痕形成主要由αSMA 细胞介导，并导致功能和结构特性永久降低。
