Diversity Supplement to R01AR072669 Utilizing Beige Fat to Improve Muscle function After Rotator Cuff Repair

项目摘要 肩袖撕裂是引起肩关节疼痛和残疾的一个非常常见的原因。起来 65岁以上的患者中有50%有旋转器的证据 袖带撕裂。此外，无症状袖带小撕裂的患者倾向于进展为 更大的有症状的撕裂小肩袖撕裂的手术修复结局良好， 但是在外科治疗中， 袖口大面积撕裂。 大量的肩袖撕裂与肩袖肌肉的脂肪浸润有关。 发生脂肪浸润的大袖带撕裂患者的临床结局较差 以及在尝试修复后的更高故障率。我们以前发现， 新发现的干细胞群--FAPs--在脂肪发育中至关重要 袖带损伤后的浸润。此外，这些细胞与其他细胞具有相似的表达模式。 米色脂肪细胞系是一种独特的细胞群，具有独特的产热和 可以改善肌肉功能的代谢能力。 这项研究将支持史蒂芬加西亚，医学博士，博士后居民在加州大学旧金山分校 骨科。他将使用我们经过充分研究的动物模型和一个 一种新的修复模型来评估FAP细胞改善肌肉的机制 通过分化成米色脂肪表型发挥功能。了解 FAP细胞和米色脂肪细胞之间的关系以及利用这些细胞 内源性和外源性治疗策略可以帮助改善肌肉质量， 袖带修复以及其他肌肉损伤状态。

Project Summary Rotator cuff tears are an extremely common cause of shoulder pain and disability. Up to 50% of patients greater than the age of 65 years of age have evidence of a rotator cuff tear. In addition, patients with small asymptomatic cuff tears tend to progress to larger, symptomatic tears. The outcomes of surgical repair of small cuff tears are good, but there has been limited success in the surgical treatment in the surgical treatment of massive cuff tears. Massive cuff tears have been linked with fatty infiltration of the rotator cuff muscles. Patients with large cuff tears who develop fatty infiltration have poorer clinical outcomes and higher rates of failure after attempted repair. We have previously found that a newly discovered stem cell population-FAPs-is critical in the development of fatty infiltration after cuff injury. Further, these cells share similar expression patterns with the beige adipocyte lineage, a distinct cell population that has unique thermogenic and metabolic capabilities that could improve muscle function. This study will support Steven Garcia, MD, a post doctoral resident in the UCSF Department of Orthopedic Surgery. He will use our well-studied animal model and a novel repair model to evaluate the mechanism by which FAP cells can improve muscle function through differentiation into a beige fat phenotype. Understanding the relationship between FAP cells and beige adipocytes and utilizing these cells in endogenous and exogenous treatment strategies could help improve muscle quality in cuff repair as well as other muscle injury states.