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

R01AR072669 的多样性补充利用米色脂肪改善肩袖修复后的肌肉功能

• 批准号: 10360786
• 负责人: Brian Feeley
• 金额: $ 12.26万
• 依托单位: NORTHERN CALIFORNIA INSTITUTE/RES/EDU
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10360786
• 关键词: Adipocytes; Adipose tissue; Affect; Age-Years; American; Animal Model; Animals; Anterior; Atrophic; Cell Differentiation process; Cell physiology; Cells; Clinical; Coculture Techniques; Data; Development; Diabetes Mellitus; Economic Burden; FRAP1 gene; Failure; Fatty acid glycerol esters; Follistatin; Gene Expression; Grant; Growth; Health Care Costs; Human; In Vitro; Infiltration; Injury; Insulin-Like Growth Factor I; Knowledge; Link; Metabolic; Molecular; Mus; Muscle; Muscle function; Muscular Atrophy; Myopathy; Operative Surgical Procedures; Orthopedic Surgery; Outcome; Outcome Study; Pathway interactions; Patient-Focused Outcomes; Patients; Pattern; Pharmacological Treatment; Pharmacology; Phenotype; Population; Postdoctoral Fellow; Process; Production; Productivity; Proliferating; Quality of life; Recovery; Role; Rotator Cuff; Shoulder Pain; Source; TGFB1 gene; Thermogenesis; Transgenic Mice; Translating; Upper Extremity; Wages; Work; adipokines; age group; aged; cell type; clinically significant; clinically translatable; disability; experimental study; gain of function; gait examination; human old age (65+); improved; injured; injury and repair; interest; limb injury; loss of function; medical attention; mouse model; muscle degeneration; muscle regeneration; novel; overexpression; parent grant; physically handicapped; repair model; repaired; rotator cuff injury; rotator cuff tear; satellite cell; stem cell population; success; supraspinatus muscle; surgery outcome; therapeutic target; treatment strategy

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.

项目概要 肩袖撕裂是肩部疼痛和残疾的一个极其常见的原因。向上 50% 65 岁以上的患者有旋转器的证据 袖口撕裂。此外，无症状袖带撕裂的患者往往会进展为 较大的、有症状的眼泪。小袖口撕裂的手术修复效果良好， 但手术治疗取得的成功有限 袖口有大量撕裂。 大量袖套撕裂与肩袖肌肉的脂肪浸润有关。 发生脂肪浸润的袖带大撕裂患者的临床结果较差 尝试修复后故障率更高。我们之前发现有一个 新发现的干细胞群 - FAP - 在脂肪细胞的发育中至关重要 袖带损伤后的浸润。此外，这些细胞与以下细胞具有相似的表达模式： 米色脂肪细胞谱系，一个独特的细胞群，具有独特的产热和 可以改善肌肉功能的代谢能力。 这项研究将支持加州大学旧金山分校博士后住院医师史蒂文·加西亚 (Steven Garcia) 博士 骨科。他将使用我们经过充分研究的动物模型和 评估 FAP 细胞改善肌肉机制的新型修复模型 通过分化成米色脂肪表型来发挥功能。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。