Metformin prevents against oxidative stress-induced senescence in human periodontal ligament cells
Metformin prevents against oxidative stress-induced senescence in human periodontal ligament cells
复制标题
二甲双胍预防氧化应激诱导的人牙周膜细胞衰老
DOI：
10.1007/s10522-019-09838-x
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发表时间：
2020-02-01
期刊：
影响因子：
4.5
通讯作者：
Song, Jinlin
中科院分区：
文献类型：
--
作者：
Kuang, Yunchun;Hu, Bo;Song, Jinlin
牙周炎是一种累及牙周组织的慢性感染性疾病。牙周膜细胞（PDLCs）在牙周组织再生中发挥着重要作用。然而，衰老的牙周膜细胞再生潜力受阻。据报道，二甲双胍在细胞和个体水平均能预防衰老。本研究旨在评估二甲双胍对氧化应激下人牙周膜细胞（hPDLCs）细胞衰老的影响。hPDLCs先用二甲双胍预处理，随后暴露于过氧化氢（H₂O₂）中。检测细胞活力、氧化损伤、细胞衰老和成骨潜力。为抑制自噬，hPDLCs在二甲双胍处理前用3 - 甲基腺嘌呤处理。本研究显示，暴露于H₂O₂会抑制hPDLCs的增殖，增加溶酶体β - 半乳糖苷酶活性，加剧活性氧（ROS）积累，加重氧化损伤，刺激衰老相关基因的表达，并阻碍hPDLCs的成骨分化活性。二甲双胍预处理可部分逆转H₂O₂对hPDLCs的有害影响。此外，二甲双胍可刺激自噬，而用3 - 甲基腺嘌呤抑制自噬则会逆转二甲双胍在氧化应激下对hPDLCs的抗衰老作用。本研究表明，二甲双胍可通过刺激自噬减轻氧化应激诱导的衰老，并能部分恢复hPDLCs的成骨潜力，这可能为从抗衰老角度探索牙周治疗提供参考。
Periodontitis is a chronic infectious disease involving periodontal tissues. Periodontal ligament cells (PDLCs) play an important role in the regeneration of periodontal tissue. However, senescent PDLCs have an impeded regenerative potential. Metformin has been reported to prevent senescence at both the cellular and individual levels. The objectives of the present study were to evaluate the effects of metformin on cellular senescence in human PDLCs (hPDLCs) under oxidative stress. hPDLCs were pretreated with metformin, followed by H2O2exposure. The cell viability, oxidative damage, cellular senescence and osteogenic potential were detected. To inhibit autophagy, hPDLCs were treated with 3-methyladenine before metformin treatment. The present study revealed that H2O2exposure inhibits proliferation, increased lysosomal β-galactosidase activity, augments reactive oxidative species (ROS) accumulation, elevates the oxidative damage, stimulates the expression of senescence-related genes and impedes the activity of the osteogenic differentiation of hPDLCs. Metformin pretreatment could partly reverse the detrimental influences of H2O2on hPDLCs. Moreover, metformin could stimulate autophagy, whereas the inhibition of autophagy with 3-methyladenine reversed the anti-senescence effects of metformin on hPDLCs under oxidative stress. The present study manifested that metformin could alleviate oxidative stress-induced senescence via stimulating autophagy and could partially recover the osteogenic potential of hPDLCs, possibly providing a reference for the discovery of periodontal treatment from the perspective of antisenescence.