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

基本信息

批准号：
10192661
负责人：
Brian Feeley
金额：
$ 32.71万
依托单位：
NORTHERN CALIFORNIA INSTITUTE/RES/EDU
依托单位国家：
美国
项目类别：
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/10192661
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 Outcome Outcome Study Pathway interactions Patient-Focused Outcomes Patients Pattern Pharmacological Treatment Pharmacology Phenotype Population Process Production Productivity Proliferating Quality of life Recovery Role Rotator Cuff Shoulder Pain Source 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 limb injury loss of function medical attention mouse model muscle degeneration muscle regeneration novel overexpression physically handicapped progenitor repair model repaired rotator cuff injury rotator cuff tear satellite cell shoulder injury stem cell population stem cells success supraspinatus muscle surgery outcome therapeutic target treatment strategy

项目摘要

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 项目描述 45 肩袖 (RC) 撕裂是肩部疼痛的一个极其常见的原因残疾。高达 50% 的 65 岁以上患者有证据 6789 RC 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 RC 撕裂的手术修复效果良好，但大面积 RC 撕裂的手术治疗取得的成功有限。 11 01 大量 RC 撕裂与肩袖肌肉的脂肪浸润有关。出现脂肪浸润的大面积 RC 撕裂患者的临床结果较差 11 23 尝试修复后故障率更高。之前我们发现有一个新的发现的干细胞群——纤维/脂肪细胞祖细胞（FAP）——在 11 45 RC 损伤后脂肪浸润的发展。此外，这些细胞具有相似的米色脂肪细胞谱系的表达模式，这是一个独特的细胞群，具有 11 67 独特的产热和代谢能力，可以改善肌肉功能。 11 89 该研究将利用我们经过充分研究的动物模型和新颖的修复模型来评估 FAP 细胞通过以下方式改善肌肉功能的机制： 22 01 在小鼠和人体组织中分化为米色脂肪表型。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 RC 修复以及其他肌肉损伤状态。