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线粒体转移可恢复脂多糖诱导的体外关节炎模型中纤维母细胞样滑膜细胞(FLS)的可塑性。

Mitochondria transfer restores fibroblasts-like synoviocytes (FLS) plasticity in LPS-induced, in vitro synovitis model.

机构信息

Department of Experimental Biology, Wroclaw University of Environmental and Life Sciences, Norwida 27B Street, A7 Building, 50-375, Wroclaw, Poland.

International Institute of Translational Medicine, Malin, Jesionowa 11, 55-114, Wisznia Mała, Poland.

出版信息

Cell Commun Signal. 2022 Sep 7;20(1):137. doi: 10.1186/s12964-022-00923-2.

DOI:10.1186/s12964-022-00923-2
PMID:36071528
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9450291/
Abstract

BACKGROUND

Synovitis (SI) is one of the most common and serious orthopedic diseases in horses of different age, breed and sex, which contributes to the development of osteoarthritis. The burden of SI includes economic loss and represents a real challenge for current veterinary health care. At the molecular level, fibroblasts-like synoviocytes (FLS) are recognized as major cell populations involved in SI pathogenesis. In the course of SI, FLSs are losing their protective and pro-regenerative cytological features, become highly proliferative and initiate various stress signaling pathways.

METHODS

Fibroblast-like synoviocytes were treated with LPS in order to generate SI in vitro model. Mitochondria were isolated from peripheral blood derived mononuclear cells and co-cultured with FLS. After 24 h of culture, cells were subjected to RT-qPCR, western blot, cytometric and confocal microscopy analysis.

RESULTS

Mitochondrial transfer (MT) was observed in vitro studies using confocal microscopy. Further studies revealed, that MT to LPS-treated FLS reduced cell proliferation, modulated apoptosis and decreased inflammatory response. Overall, MT Resulted in the considerable recovery of recipient cells cytophysiological properties.

CONCLUSIONS

Presented data provides evidence that mitochondria transfersignificantly modulate FLS proliferative and metabolic activity through improved mitochondrial biogenesis and dynamics in activated FLS. Obtained results for the first time demonstrate that horizontal MT might be considered as a therapeutic tool for synovitis treatment; however, further clinical studies are strongly required. Video abstract.

摘要

背景

滑膜炎(SI)是不同年龄、品种和性别的马中最常见和最严重的骨科疾病之一,它会导致骨关节炎的发展。SI 的负担包括经济损失,这对当前兽医保健提出了真正的挑战。在分子水平上,成纤维样滑膜细胞(FLS)被认为是参与 SI 发病机制的主要细胞群体。在 SI 过程中,FLSs 失去了其保护和促再生的细胞学特征,变得高度增殖并启动各种应激信号通路。

方法

用 LPS 处理成纤维样滑膜细胞,以在体外建立 SI 模型。从外周血单核细胞中分离出线粒体,并与 FLS 共培养。培养 24 小时后,进行 RT-qPCR、western blot、细胞计数和共聚焦显微镜分析。

结果

使用共聚焦显微镜在体外研究中观察到线粒体转移(MT)。进一步的研究表明,MT 到 LPS 处理的 FLS 减少了细胞增殖,调节了细胞凋亡并降低了炎症反应。总的来说,MT 使受体细胞的细胞生理特性得到了显著恢复。

结论

目前的数据提供了证据,表明线粒体转移通过改善激活的 FLS 中线粒体的生物发生和动力学,显著调节 FLS 的增殖和代谢活性。研究结果首次表明,水平 MT 可能被视为治疗滑膜炎的一种治疗工具;然而,还需要进行更多的临床研究。视频摘要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b02/9450291/54e3c84a7a22/12964_2022_923_Fig7a_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b02/9450291/8242f419418f/12964_2022_923_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b02/9450291/6e52c155093f/12964_2022_923_Fig2a_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b02/9450291/2a0ee2828d18/12964_2022_923_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b02/9450291/cfa0c01d54c6/12964_2022_923_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b02/9450291/a6af3b37f31e/12964_2022_923_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b02/9450291/a21629d6b79d/12964_2022_923_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b02/9450291/54e3c84a7a22/12964_2022_923_Fig7a_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b02/9450291/8242f419418f/12964_2022_923_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b02/9450291/6e52c155093f/12964_2022_923_Fig2a_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b02/9450291/2a0ee2828d18/12964_2022_923_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b02/9450291/cfa0c01d54c6/12964_2022_923_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b02/9450291/a6af3b37f31e/12964_2022_923_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b02/9450291/a21629d6b79d/12964_2022_923_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b02/9450291/54e3c84a7a22/12964_2022_923_Fig7a_HTML.jpg

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