Abstract：
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.
摘要：
慢性肩袖（RC）损伤可导致有利于慢性炎症的退行性微环境，纤维化，和脂肪渗透。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,纤维脂肪原祖细胞（FAP），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以调节功能的再生和恢复，特别是来自棕色或米色脂肪（BAT）的促肌源性信号。在这项研究中,我们试图使用RCBAT移植小鼠模型鉴定肌肉再生过程中BAT信号的细胞靶标。当移植外源BAT时，心脏毒素损伤的冈上肌在手术后7天（dps）的质量得到改善。转录分析显示移植的BAT可能通过与免疫细胞的串扰在再生早期调节FAP信号传导。然而,由于28dps时肌肉质量和功能没有改善,因此没有长期获益.为了消除内源性BAT的混杂效应，我们将BAT移植到“无BAT”解偶联蛋白-1白喉毒素片段A（UCP1-DTA）小鼠中，发现肌肉收缩功能得到改善，但不是28dps的质量。有趣的是,移植的BAT增加了所有实验组的脂肪浸润，暗示再生过程中FAP脂肪生成的调节。因此，我们得出结论，移植的BAT在再生早期调节FAP信号，但不提供长期福利。
