Department of Orthopaedic Surgery, University of California, San Francisco, San Francisco, California, USA.
San Francisco Veteran Affairs Health Care System, San Francisco, California, USA.
Am J Sports Med. 2022 Jan;50(1):208-215. doi: 10.1177/03635465211054512. Epub 2021 Nov 15.
Fatty infiltration of rotator cuff muscle is a limiting factor in the success of repairs. Fibroadipogenic progenitors (FAPs) are a population of stem cells within the rotator cuff that can differentiate into white adipocytes, fibroblasts, and beige adipocytes. The effects of patient age and rotator cuff tendon tear size on the number, differentiation patterns, and gene expression profiles of FAPs have not yet been analyzed.
To determine if patient age and rotator cuff tear size independently regulate FAP number, differentiation patterns, and gene expression profiles.
Controlled laboratory study.
Supraspinatus muscle samples were collected from 26 patients between the ages of 42 and 76 years with partial- or full-thickness rotator cuff tears. FAPs were quantified using fluorescence-activated cell sorting. Gene expression analysis was performed across a custom 96-gene panel using NanoString. In vitro differentiation assays of FAPs were conducted using adipogenic, fibrogenic, and beige-inducing (amibegron-treated) media, and quantitative polymerase chain reaction was used to assess gene expression differences between adipogenic and amibegron media conditions. Multivariable linear regressions were performed using Stata to independently analyze the effects of age and rotator cuff tear size on FAP number, differentiation, and gene expression.
Increasing age and tear size were independently correlated with increased FAP number (β = 0.21, = .03; β = 3.86, = .05). There was no clear association between age and gene expression of freshly sorted FAPs. Under adipogenic and fibrogenic media conditions, increasing age and tear size were independently associated with increased adipogenic and fibrogenic differentiation of FAPs. Under amibegron treatment conditions, age positively correlated with increased beige differentiation (β = 1.03; < .0001), while increasing tear size showed a trend toward decreased beige differentiation (β = -4.87; = .1). When gene expression patterns between adipogenic and amibegron media conditions were compared, larger tear size strongly inhibited beige gene expression, while advanced age did not.
Patient age and rotator cuff tear size independently regulated FAP number, differentiation, and gene expression. Age and tear size were positively correlated with increased FAP number and fibrogenic/adipogenic differentiation. Advancing patient age did not limit FAP beige differentiation and gene expression, while increasing rotator cuff tear size strongly inhibited these processes.
肩袖肌肉脂肪浸润是修复成功的限制因素。纤维脂肪祖细胞（FAP）是肩袖内的一种干细胞群，可分化为白色脂肪细胞、成纤维细胞和米色脂肪细胞。患者年龄和肩袖肌腱撕裂大小对 FAP 的数量、分化模式和基因表达谱的影响尚未进行分析。
确定患者年龄和肩袖撕裂大小是否独立调节 FAP 的数量、分化模式和基因表达谱。
对照实验室研究。
从 42 岁至 76 岁之间的 26 名部分或全层肩袖撕裂患者中采集冈上肌样本。使用荧光激活细胞分选术定量 FAP。使用 NanoString 对定制的 96 基因面板进行基因表达分析。使用成脂、成纤维和米色诱导（阿米贝隆处理）培养基进行 FAP 的体外分化实验，并使用定量聚合酶链反应评估成脂和阿米贝隆培养基条件之间基因表达的差异。使用 Stata 进行多变量线性回归，分别分析年龄和肩袖撕裂大小对 FAP 数量、分化和基因表达的影响。
年龄增加和撕裂增大与 FAP 数量增加独立相关（β=0.21，P=.03；β=3.86，P=.05）。年龄与新鲜分选 FAP 的基因表达之间没有明显的关联。在成脂和成纤维培养基条件下，年龄增加和撕裂增大与 FAP 的成脂和成纤维分化增加独立相关。在阿米贝隆处理条件下，年龄与米色分化增加呈正相关（β=1.03；P<.0001），而撕裂增大则呈米色分化减少的趋势（β=-4.87；P=.1）。当比较成脂和阿米贝隆培养基条件下的基因表达模式时，较大的撕裂大小强烈抑制米色基因表达，而年龄增加则没有。
患者年龄和肩袖撕裂大小独立调节 FAP 的数量、分化和基因表达。年龄和撕裂大小与 FAP 数量增加以及成纤维/成脂分化增加呈正相关。患者年龄增加不会限制 FAP 的米色分化和基因表达，而增加肩袖撕裂大小则强烈抑制这些过程。
