Utilizing beige fat to improve muscle function after rotator cuff repair

利用米色脂肪改善肩袖修复后的肌肉功能

• 批准号: 9767659
• 负责人: Brian Feeley
• 金额: $ 33.73万
• 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/9767659
• 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; Modeling; Molecular; Mus; Muscle; Muscle function; Muscular Atrophy; Myopathy; Operative Surgical Procedures; Outcome; Outcome Study; Pathway interactions; Patient-Focused Outcomes; Patients; Pattern; Pharmacological Treatment; Pharmacology; Phenotype; Physically Handicapped; Population; Process; Production; Productivity; Proliferating; Quality of life; Recovery; Role; Rotator Cuff; Shoulder; Shoulder Pain; Source; Stem cells; 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+); human tissue; improved; injured; injury and repair; interest; loss of function; medical attention; mouse model; muscle degeneration; muscle regeneration; novel; overexpression; progenitor; repaired; rotator cuff injury; rotator cuff tear; satellite cell; stem cell population; success; supraspinatus muscle; surgery outcome; therapeutic target; treatment strategy

123 PROJECT DESCRIPTION 45 Rotator cuff (RC) 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 6789 of a RC tear. In addition, patients with small asymptomatic cuff tears tend to progress to larger, symptomatic tears. The outcomes of surgical repair of small RC tears are good, but there has been limited success in the surgical treatment of massive RC tears. 11 01 Massive RC tears have been linked with fatty infiltration of the rotator cuff muscles. Patients with large RC tears who develop fatty infiltration have poorer clinical outcomes 11 23 and higher rates of failure after attempted repair. We have previously found that a newly discovered stem cell population-fibro/adipocyte progenitor (FAP) cells-is critical in the 11 45 development of fatty infiltration after RC injury. Further, these cells share similar expression patterns with the beige adipocyte lineage, a distinct cell population that has 11 67 unique thermogenic and metabolic capabilities that could improve muscle function. 11 89 The study will leverage our well-studied animal model and a novel repair model to evaluate the mechanism by which FAP cells can improve muscle function through 22 01 differentiation into a beige fat phenotype in mouse and human tissue. 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 RC repair as well as other muscle injury states.

123 项目说明 45 肩袖撕裂是导致肩痛的一种非常常见的原因 残疾。高达50%的65岁以上的患者有证据 六七八九 钢筋混凝土撕裂的痕迹。此外，小的无症状袖带撕裂的患者倾向于进展到 更大的，有症状的泪水。小裂孔的手术修复效果良好， 但在手术治疗巨大的RC撕裂方面取得的成功是有限的。 11 01 大量的RC撕裂与肩袖肌肉的脂肪渗透有关。 伴有较大的RC撕裂并发展为脂肪渗透的患者的临床预后较差 11 23 并且尝试修复后的故障率更高。我们之前发现了一个新的 已发现的干细胞群体-纤维/脂肪祖细胞(FAP)-在 11 45 RC损伤后脂肪渗出的发展。此外，这些细胞具有相似的 米色脂肪细胞谱系的表达模式，一个独特的细胞群体 11 67 独特的生热和新陈代谢能力，可以改善肌肉功能。 11 这项研究将利用我们研究充分的动物模型和一种新的修复模型来 评估FAP细胞通过以下途径改善肌肉功能的机制 22 01 在小鼠和人类组织中分化为米色脂肪表型。了解 FAP细胞与米色脂肪细胞的关系及其在临床中的应用 内源性和外源性治疗策略可以帮助改善肌肉质量 RC修复以及其他肌肉损伤状态。