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二甲双胍通过 AMPK 依赖性自噬通路改善脂肪间充质干细胞衰老并减轻骨关节炎进展。

Metformin Ameliorates Senescence of Adipose-Derived Mesenchymal Stem Cells and Attenuates Osteoarthritis Progression via the AMPK-Dependent Autophagy Pathway.

机构信息

Department of Orthopedics, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Department of Joint Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, China.

出版信息

Oxid Med Cell Longev. 2022 Jun 3;2022:4620254. doi: 10.1155/2022/4620254. eCollection 2022.

DOI:10.1155/2022/4620254
PMID:35693701
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9187432/
Abstract

Osteoarthritis (OA) is one of the most serious age-related diseases worldwide that drastically affects the quality of life of patients. Despite advancements in the treatment of arthritis, especially with adipose-derived mesenchymal stem cells (ADSCs), senescence-induced alterations in ADSCs negatively affect the treatment outcomes. This study was aimed at mechanistically exploring whether metformin could ameliorate the senescence of ADSCs and at exploring the effect of metformin-preconditioned ADSCs in an experimental OA mouse model. In this study, an HO-induced mouse ADSC senescent model was established. Cell proliferation, senescence, and autophagy were investigated in vitro. Moreover, the effects of intra-articular injection of metformin-preconditioned ADSCs were investigated in vivo. Metformin could promote autophagy and activate the AMPK/mTOR pathway in ADSCs. The metformin-enhanced autophagy could improve the survival and reduce the senescence of ADSCs. The protective effects of metformin against senescence were partially blocked by 3-methyladenine and compound C. Injection of metformin-preconditioned ADSCs slowed OA progression and reduced OA pain in mice. The results suggest that metformin activates the AMPK/mTOR-dependent autophagy pathway in ADSCs against HO-induced senescence, while metformin-preconditioned ADSCs can potentially inhibit OA progression.

摘要

骨关节炎（OA）是全球范围内最严重的与年龄相关的疾病之一，严重影响患者的生活质量。尽管关节炎的治疗取得了进展，特别是脂肪来源间充质干细胞（ADSCs）的治疗，但 ADSC 衰老引起的变化会对治疗效果产生负面影响。本研究旨在从机制上探讨二甲双胍是否可以改善 ADSC 的衰老，并探讨二甲双胍预处理的 ADSC 在实验性 OA 小鼠模型中的作用。在这项研究中，建立了 HO 诱导的小鼠 ADSC 衰老模型。在体外研究了细胞增殖、衰老和自噬。此外，还研究了关节内注射二甲双胍预处理的 ADSC 的体内作用。二甲双胍可以促进 ADSC 中的自噬并激活 AMPK/mTOR 通路。二甲双胍增强的自噬可以提高 ADSC 的存活率并减少衰老。3-甲基腺嘌呤和化合物 C 部分阻断了二甲双胍对衰老的保护作用。注射二甲双胍预处理的 ADSC 可减缓 OA 进展并减轻小鼠的 OA 疼痛。结果表明，二甲双胍激活 ADSC 中的 AMPK/mTOR 依赖性自噬途径以抵抗 HO 诱导的衰老，而二甲双胍预处理的 ADSC 可能抑制 OA 的进展。

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3
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