在小鼠胫骨前肌切断模型中,纤维脂肪生成祖细胞可在肌腱断裂后的急性期预防骨骼肌退化。

Fibro-adipogenic progenitors prevent skeletal muscle degeneration at acute phase upon tendon rupture in a murine tibialis anterior tenotomy model.

作者信息

Ding Zhe-Ci, He Juan-Juan, Shi Lu-Ze, Qian Jin, Mei Shu-Hao, Kang Xia, Chen Ji-Wu

机构信息

Department of Sports Medicine, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai 200080, China.

Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China.

出版信息

World J Stem Cells. 2025 Jun 26;17(6):105491. doi: 10.4252/wjsc.v17.i6.105491.

Abstract

BACKGROUND

Fibro-adipogenic progenitors (FAPs) are a group of mesenchymal stem cells that cause fibro-fatty degeneration in skeletal muscle in various chronic disease models. FAPs also play a role in preventing muscle degeneration at acute stages during disease progression. However, few studies have reported the changes in and function of FAPs in the acute phase after tendon rupture.

AIM

To clarify the changes in the number of FAPs and their impact on skeletal muscle soon after tendon rupture to facilitate future studies targeting FAPs to treat muscle degeneration.

METHODS

We utilized Pdgfra-H2B::eGFP mice to trace and quantify FAPs in a tibialis anterior tenotomy (TAT) model at 0 and 3 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, and 6 weeks post-injury, and the results were further validated using fluorescence-activated cell sorting analysis with C57BL/6 mice at the same post-injury timepoints. We subsequently used PdgfraCre::Rosa mice, and evaluated the severity of post-TAT skeletal muscle degeneration with or without FAP-depletion.

RESULTS

The number of FAPs peaked at 1 week post-TAT before gradually declining to a level comparable to that pre-TAT. The change in the number of FAPs was potentially temporally correlated with the progression of skeletal muscle degeneration after TAT. FAP-depletion led to more severe degeneration early after TAT, indicating that FAPs potentially alleviate muscle degeneration after tendon rupture in the early post-injury phase.

CONCLUSION

FAPs potentially alleviate the degeneration of skeletal muscle in the acute stage after tendon rupture.

摘要

背景

成纤维脂肪祖细胞(FAPs)是一群间充质干细胞,在各种慢性疾病模型中可导致骨骼肌发生纤维脂肪变性。在疾病进展的急性期,FAPs在预防肌肉变性方面也发挥作用。然而,很少有研究报道肌腱断裂急性期FAPs的变化及其功能。

目的

明确肌腱断裂后不久FAPs数量的变化及其对骨骼肌的影响,以促进未来针对FAPs治疗肌肉变性的研究。

方法

我们利用Pdgfra-H2B::eGFP小鼠,在损伤后0天、3天、1周、2周、3周、4周、5周和6周的胫骨前肌切断术(TAT)模型中追踪和量化FAPs,并用C57BL/6小鼠在相同损伤后时间点进行荧光激活细胞分选分析进一步验证结果。随后,我们使用PdgfraCre::Rosa小鼠,评估有无FAPs缺失时TAT后骨骼肌变性的严重程度。

结果

FAPs数量在TAT后1周达到峰值,随后逐渐下降至与TAT前相当的水平。FAPs数量的变化可能与TAT后骨骼肌变性的进展在时间上相关。FAPs缺失导致TAT后早期更严重的变性,表明FAPs在损伤后早期可能减轻肌腱断裂后的肌肉变性。

结论

FAPs可能减轻肌腱断裂后急性期骨骼肌的变性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5841/12203131/33d1cebd5a6d/wjsc-17-6-105491-g002.jpg

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