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引用次数: 0
摘要
慢性肩袖(RC)损伤可导致一种有利于慢性炎症、纤维化和脂肪浸润的退行性微环境。肌肉结构和功能的恢复最终需要一个复杂的肌肉驻留细胞网络,包括卫星细胞、纤维-脂肪生成祖细胞(FAPs)和免疫细胞。最近的研究表明,来自脂肪组织和祖细胞的信号可调节再生和功能恢复,尤其是来自棕色或米色脂肪(BAT)的原生信号。在这项研究中,我们试图利用 RC BAT 移植小鼠模型来确定肌肉再生过程中 BAT 信号的细胞靶点。心肌毒素损伤的冈上肌在移植外源性 BAT 后,其质量在术后 7 天(dps)得到改善。转录分析表明,移植的 BAT 可能通过与免疫细胞串扰,在再生早期调节 FAP 信号。然而,这并没有带来长期的益处,因为肌肉质量和功能在 28 dps 时并没有得到改善。为了消除内源性 BAT 的干扰效应,我们将 BAT 移植到 "无 BAT "解偶联蛋白-1 白喉毒素片段 A(UCP1-DTA)小鼠体内,结果发现 28 dps 时肌肉收缩功能得到改善,但肌肉质量没有改善。有趣的是,移植的 BAT 增加了所有实验组的脂肪浸润,这意味着在再生过程中 FAP 的脂肪生成受到了调节。因此,我们得出结论:移植的 BAT 可在再生早期调节 FAP 信号,但不会带来长期益处。
Transcriptional evidence for transient regulation of muscle regeneration by brown adipose transplant in the rotator cuff
Chronic rotator cuff (RC) injuries can lead to a degenerative microenvironment that favors chronic inflammation, fibrosis, and fatty infiltration. Recovery of muscle structure and function will ultimately require a complex network of muscle resident cells, including satellite cells, fibro-adipogenic progenitors (FAPs), and immune cells. Recent work suggests that signaling from adipose tissue and progenitors could modulate regeneration and recovery of function, particularly promyogenic signaling from brown or beige adipose (BAT). In this study, we sought to identify cellular targets of BAT signaling during muscle regeneration using a RC BAT transplantation mouse model. Cardiotoxin injured supraspinatus muscle had improved mass at 7 days postsurgery (dps) when transplanted with exogeneous BAT. Transcriptional analysis revealed transplanted BAT modulates FAP signaling early in regeneration likely via crosstalk with immune cells. However, this conferred no long-term benefit as muscle mass and function were not improved at 28 dps. To eliminate the confounding effects of endogenous BAT, we transplanted BAT in the “BAT-free” uncoupling protein-1 diphtheria toxin fragment A (UCP1-DTA) mouse and here found improved muscle contractile function, but not mass at 28 dps. Interestingly, the transplanted BAT increased fatty infiltration in all experimental groups, implying modulation of FAP adipogenesis during regeneration. Thus, we conclude that transplanted BAT modulates FAP signaling early in regeneration, but does not grant long-term benefits.
期刊介绍:
The Journal of Orthopaedic Research is the forum for the rapid publication of high quality reports of new information on the full spectrum of orthopaedic research, including life sciences, engineering, translational, and clinical studies.