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二甲双胍增强人牙周膜干细胞来源的细胞外囊泡对牙周炎的治疗效果。

Metformin enhances the therapeutic effects of extracellular vesicles derived from human periodontal ligament stem cells on periodontitis.

机构信息

GuiZhou University Medical College, Guiyang, 550025, Guizhou Province, China.

Oral Disease Research Key Laboratory of Guizhou Tertiary Institution, School of Stomatology, Zunyi Medical University, Zunyi, 563006, China.

出版信息

Sci Rep. 2024 Aug 27;14(1):19940. doi: 10.1038/s41598-024-70688-w.

DOI:10.1038/s41598-024-70688-w
PMID:39198490
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11358454/
Abstract

Metformin has shown outstanding anti-inflammatory and osteogenic abilities. Mesenchymal stem cell-derived extracellular vesicles (EVs) reveal promising therapeutic potency by carrying various biomolecules. This study explored the effects of metformin on the therapeutic potential of EVs derived from human periodontal ligament stem cells (PDLSCs) for periodontitis. PDLSCs were cultured in osteogenic medium with or without metformin, and the supernatant was then collected separately to extract EVs and metformin-treated EVs (M-EVs). After identifying the characteristics, we evaluated the anti-inflammatory and osteogenic effects of EVs and M-EVs in vivo and in vitro. Osteogenic differentiation of PDLSCs was markedly enhanced after metformin treatment, and the effect was dramatically inhibited by GW4896, an inhibitor of EVs' secretion. Metformin significantly increased EVs' yields and improved their effects on cell proliferation, migration, and osteogenic differentiation. Moreover, metformin significantly enhanced the osteogenic ability of EVs on inflammatory PDLSCs. Animal experiments revealed that alveolar bone resorption was dramatically reduced in the EVs and M-EVs groups when compared to the periodontitis group, while the M-EVs group showed the lowest levels of alveolar bone loss. Metformin promoted the osteogenic differentiation of PDLSCs partly through EVs pathway and significantly enhanced the secretion of PDLSCs-EVs with superior pro-osteogenic and anti-inflammatory potential, thus improving EVs' therapeutic potential on periodontitis.

摘要

二甲双胍具有出色的抗炎和成骨能力。间充质干细胞衍生的细胞外囊泡（EVs）通过携带各种生物分子显示出有希望的治疗潜力。本研究探讨了二甲双胍对人牙周膜干细胞（PDLSCs）衍生的 EVs 治疗牙周炎的治疗潜力的影响。将 PDLSCs 在成骨培养基中培养，有或没有二甲双胍，然后分别收集上清液以提取 EVs 和二甲双胍处理的 EVs（M-EVs）。在鉴定特征后，我们评估了 EVs 和 M-EVs 在体内和体外的抗炎和成骨作用。二甲双胍处理后，PDLSCs 的成骨分化明显增强，而 EVs 分泌抑制剂 GW4896 则显著抑制了这种作用。二甲双胍显著增加了 EVs 的产量，并改善了它们对细胞增殖、迁移和成骨分化的作用。此外，二甲双胍显著增强了 EVs 对炎症性 PDLSCs 的成骨能力。动物实验表明，与牙周炎组相比，EVs 和 M-EVs 组的牙槽骨吸收明显减少，而 M-EVs 组的牙槽骨丢失水平最低。二甲双胍通过 EVs 途径促进 PDLSCs 的成骨分化，并显著增强具有优越的促成骨和抗炎潜力的 PDLSCs-EVs 的分泌，从而提高 EVs 对牙周炎的治疗潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4e6/11358454/333028c9f287/41598_2024_70688_Fig7_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4e6/11358454/333028c9f287/41598_2024_70688_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4e6/11358454/f422a4e0c1d5/41598_2024_70688_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4e6/11358454/61b113917736/41598_2024_70688_Fig2_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4e6/11358454/c7656dd44b40/41598_2024_70688_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4e6/11358454/6eac1488b9e4/41598_2024_70688_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4e6/11358454/333028c9f287/41598_2024_70688_Fig7_HTML.jpg

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Bomidin attenuates inflammation of periodontal ligament stem cells and periodontitis in mice via inhibiting ferroptosis.波米定通过抑制铁死亡减轻小鼠牙周膜干细胞炎症和牙周炎。
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Skeletal muscle-derived extracellular vesicles transport glycolytic enzymes to mediate muscle-to-bone crosstalk.
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Flavonoid extract from propolis alleviates periodontitis by boosting periodontium regeneration and inflammation resolution via regulating TLR4/MyD88/NF-κB and RANK/NF-κB pathway.蜂胶中的类黄酮提取物通过调节 TLR4/MyD88/NF-κB 和 RANK/NF-κB 通路促进牙周组织再生和炎症缓解来缓解牙周炎。
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The Differential Effect of Metformin on Osteocytes, Osteoblasts, and Osteoclasts.二甲双胍对骨细胞、成骨细胞和破骨细胞的差异作用。
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