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脂肪间充质干细胞通过上调 BTG2 在骨关节炎中的新治疗机制。

Novel Therapeutic Mechanism of Adipose-Derived Mesenchymal Stem Cells in Osteoarthritis via Upregulation of BTG2.

机构信息

State Key Laboratory of Quality Research in Chinese Medicine & School of Pharmacy, Macau University of Science and Technology, Taipa, China.

Department of Hepatabiliary and Pancreatic Surgery Center, Cell Transplantation Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.

出版信息

Oxid Med Cell Longev. 2022 Oct 15;2022:9252319. doi: 10.1155/2022/9252319. eCollection 2022.

DOI:10.1155/2022/9252319
PMID:36299602
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9590117/
Abstract

BACKGROUND

Osteoarthritis (OA) is a debilitating and degenerative joint disease, which is characterized by progressive destruction of articular cartilage. Mesenchymal stem cells (MSCs) have been implicated in the treatment of OA. However, the function of adipose-derived MSCs (AD-MSCs) in OA and its underlying mechanism remain obscure.

AIM

We aimed to explore the function of AD-MSCs in OA and investigate its potential regulatory mechanism.

METHODS

A guinea pig model of OA was constructed. AD-MSCs injected into the articular cavity of OA guinea pigs were viewed by bioluminescence imaging. The effect of AD-MSCs on the gonarthritis of OA guinea pigs was evaluated through both macroscopic and microscopic detections. The detailed molecular mechanism was predicted by GEO databases and bioinformatics tools and then verified via mechanism experiments, including ChIP assay, DNA pulldown assay, and luciferase reporter assay.

RESULTS

AD-MSCs had a significant positive therapeutic effect on the gonarthritis of the OA model, and the overall effects of it was better than that of sodium hyaluronate (SH). B-cell translocation gene 2 (BTG2) was significantly downregulated in the articular cartilage of the OA guinea pigs. Furthermore, BTG2 was positively regulated by Krüppel-like factor 4 (KLF4) in AD-MSCs at the transcriptional level. AD-MSCs performed an effect on KLF4 expression at the transcriptional levels.

CONCLUSION

AD-MSCs suppresses OA progression through KLF4-induced transcriptional activation of BTG2. Our findings revealed an AD-MSCs-dominated therapeutic method for OA.

摘要

背景

骨关节炎（OA）是一种使人衰弱和退行性的关节疾病，其特征是关节软骨的进行性破坏。间充质干细胞（MSCs）已被认为与 OA 的治疗有关。然而，脂肪来源的间充质干细胞（AD-MSCs）在 OA 中的功能及其潜在的调节机制仍不清楚。

目的

我们旨在探讨 AD-MSCs 在 OA 中的功能，并研究其潜在的调节机制。

方法

构建了 OA 豚鼠模型。通过生物发光成像观察注射到 OA 豚鼠关节腔内的 AD-MSCs。通过宏观和微观检测评估 AD-MSCs 对 OA 豚鼠关节炎的影响。通过 GEO 数据库和生物信息学工具预测详细的分子机制，并通过机制实验进行验证，包括 ChIP 测定、DNA 下拉测定和荧光素酶报告基因测定。

结果

AD-MSCs 对 OA 模型的关节炎有显著的积极治疗作用，其总体效果优于透明质酸钠（SH）。BTG2 在 OA 豚鼠的关节软骨中明显下调。此外，AD-MSCs 中 BTG2 在转录水平上受 Krüppel 样因子 4（KLF4）的正向调节。AD-MSCs 在转录水平上对 KLF4 表达有影响。

结论

AD-MSCs 通过 KLF4 诱导的 BTG2 转录激活抑制 OA 进展。我们的研究结果揭示了 AD-MSCs 主导的 OA 治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69ff/9590117/d035884e0dbf/OMCL2022-9252319.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69ff/9590117/7411dcbb97d2/OMCL2022-9252319.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69ff/9590117/073641e68537/OMCL2022-9252319.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69ff/9590117/2649dbcba0db/OMCL2022-9252319.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69ff/9590117/0a66e0893225/OMCL2022-9252319.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69ff/9590117/0f9251761ed3/OMCL2022-9252319.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69ff/9590117/d035884e0dbf/OMCL2022-9252319.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69ff/9590117/7411dcbb97d2/OMCL2022-9252319.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69ff/9590117/073641e68537/OMCL2022-9252319.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69ff/9590117/2649dbcba0db/OMCL2022-9252319.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69ff/9590117/0a66e0893225/OMCL2022-9252319.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69ff/9590117/0f9251761ed3/OMCL2022-9252319.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69ff/9590117/d035884e0dbf/OMCL2022-9252319.006.jpg

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