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丙酸杆菌 MJ2 衍生的细胞外囊泡抑制 RANKL 诱导的破骨细胞生成并改善胶原诱导的类风湿关节炎。

Propionibacterium freudenreichii MJ2-derived extracellular vesicles inhibit RANKL-induced osteoclastogenesis and improve collagen-induced rheumatoid arthritis.

机构信息

Department of Integrated Biomedical and Life Sciences, Graduate School, Korea University, Seoul, 02841, Republic of Korea.

School of Biosystems and Biomedical Sciences, Korea University, Seoul, 02841, Republic of Korea.

出版信息

Sci Rep. 2024 Oct 23;14(1):24973. doi: 10.1038/s41598-024-76911-y.

DOI:10.1038/s41598-024-76911-y
PMID:39443658
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11500175/
Abstract

Rheumatoid arthritis causes excessive bone loss by stimulating osteoclast differentiation. Extracellular vesicles are valuable disease markers, conveyors of distant cell-to-cell communication, and carriers for drug delivery. The aim of this study was to investigate the anti-osteoclastogenic effects of extracellular vesicles derived from dairy Propionibacterium freudenreichii MJ2 (PFEVs) and the improvement effect of PFEVs on collagen-induced arthritis (CIA) animal model. PFEVs were observed by scanning electron microscopy, transmission electron microscopy, nanoparticle tracking analysis, and LC-MS/MS. The inhibitory activity of PFEVs against receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclast differentiation was investigated in RAW 264.7 cells. PFEVs significantly decreased the expression levels of genes and proteins related to osteoclast differentiation. PFEVs decreased RANK-RANKL binding. In a CIA mouse model, PFEVs treatment significantly reduced arthritis scores and collagen-specific immunoglobulins. PFEVs treatment also reduced pro-inflammatory cytokines and increased anti-inflammatory cytokines. The anti-inflammatory effects were confirmed by H&E staining, and PFEVs treatment inhibited osteoclastogenesis in the CIA mouse model. In conclusion, PFEVs inhibited osteoclast differentiation by inhibiting RANK-RANKL signaling, thereby decreasing the expression of osteoclast differentiation-related genes. PFEVs also improved collagen-induced arthritis by inhibiting inflammation and osteoclastogenesis.

摘要

类风湿关节炎通过刺激破骨细胞分化导致过度的骨质流失。细胞外囊泡是有价值的疾病标志物,是远距离细胞间通讯的载体,也是药物递送的载体。本研究旨在探讨源自乳丙酸杆菌 MJ2(PFEVs)的细胞外囊泡对破骨细胞生成的抑制作用及其对胶原诱导性关节炎(CIA)动物模型的改善作用。通过扫描电子显微镜、透射电子显微镜、纳米颗粒跟踪分析和 LC-MS/MS 观察 PFEVs。在 RAW 264.7 细胞中研究了 PFEVs 对核因子 kappa-B 配体(RANKL)诱导的破骨细胞分化的抑制活性。PFEVs 显著降低了与破骨细胞分化相关的基因和蛋白的表达水平。PFEVs 减少了 RANK-RANKL 结合。在 CIA 小鼠模型中,PFEVs 治疗显著降低了关节炎评分和胶原特异性免疫球蛋白。PFEVs 治疗还降低了促炎细胞因子并增加了抗炎细胞因子。H&E 染色证实了抗炎作用,PFEVs 治疗抑制了 CIA 小鼠模型中的破骨细胞生成。总之,PFEVs 通过抑制 RANK-RANKL 信号通路抑制破骨细胞分化,从而降低破骨细胞分化相关基因的表达。PFEVs 还通过抑制炎症和破骨细胞生成改善胶原诱导性关节炎。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4999/11500175/90dc616e314c/41598_2024_76911_Fig7_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4999/11500175/90dc616e314c/41598_2024_76911_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4999/11500175/f92c20bc9d20/41598_2024_76911_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4999/11500175/a8cb00ca1056/41598_2024_76911_Fig2_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4999/11500175/32d48cd0aabf/41598_2024_76911_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4999/11500175/c17e94cc94d3/41598_2024_76911_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4999/11500175/90dc616e314c/41598_2024_76911_Fig7_HTML.jpg

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