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GPX7 通过铁死亡介导的机制,减少了由 IL-1β 触发的软骨细胞炎症和细胞外基质降解。

GPX7 reduces chondrocyte inflammation and extracellular matrix degradation triggered by IL‑1β, via a mechanism mediated by ferroptosis.

机构信息

Department of Physical Education, Henan University of Science and Technology, Luoyang, Henan 471023, P.R. China.

Integrative Exercise Physiology Laboratory, Department of Physical Education, Jeonbuk National University, Jeonju 54896, Republic of Korea.

出版信息

Mol Med Rep. 2024 Jul;30(1). doi: 10.3892/mmr.2024.13242. Epub 2024 May 17.

Abstract

During osteoarthritis (OA), chondrocytes become highly active, with increased matrix synthesis and inflammatory cytokine‑induced catabolic pathways. Early intervention strategies targeting pathological changes may attenuate or halt disease progression. The present study aimed to reveal the role of glutathione peroxidase (GPX)7 in OA. For this purpose, a research model was established by inducing C28/I2 human chondrocytes with interleukin (IL)‑1β, and the expression level of GPX7 was determined. To explore its roles, C28/I2 cells were transfected to gain GPX7 overexpression. The effects of GPX7 overexpression on intracellular inflammation, extracellular matrix (ECM) degradation, apoptosis and ferroptosis were then evaluated. In addition, the cells were treated with the ferroptosis inducer, erastin, and its effects on the aforementioned phenotypes were assessed. The level of GPX7 was decreased in response to IL‑1β treatment, and GPX7 overexpression suppressed cellular inflammation, ECM degradation and apoptosis. Moreover, the reduction of lipid peroxidation, ferrous ions and transferrin indicated that GPX7 overexpression inhibited ferroptosis. Subsequently, inflammation, ECM degradation and apoptosis were found to be promoted in the cells upon treatment with erastin. These findings suggested that the regulatory role of GPX7 may be mediated by a pathway involving ferroptosis. On the whole, the present study revealed that GPX7 reduces IL‑1β‑induced chondrocyte inflammation, apoptosis and ECM degradation partially through a mechanism involving ferroptosis. The results of the present study lay a theoretical foundation for subsequent OA‑related research and may enable the development of translational strategies for the treatment of OA.

摘要

在骨关节炎(OA)中,软骨细胞变得高度活跃,基质合成增加,炎症细胞因子诱导的分解代谢途径被激活。针对病理变化的早期干预策略可能会减弱或阻止疾病的进展。本研究旨在揭示谷胱甘肽过氧化物酶(GPX)7 在 OA 中的作用。为此,通过用白细胞介素(IL)-1β诱导 C28/I2 人软骨细胞,建立了研究模型,并测定了 GPX7 的表达水平。为了探讨其作用,转染 C28/I2 细胞以获得 GPX7 的过表达。然后评估 GPX7 过表达对细胞内炎症、细胞外基质(ECM)降解、细胞凋亡和铁死亡的影响。此外,用铁死亡诱导剂 erastin 处理细胞,并评估其对上述表型的影响。结果显示,IL-1β处理后 GPX7 水平降低,GPX7 过表达抑制细胞炎症、ECM 降解和细胞凋亡。此外,脂质过氧化、亚铁离子和转铁蛋白的减少表明 GPX7 过表达抑制铁死亡。随后,用 erastin 处理细胞后,发现炎症、ECM 降解和细胞凋亡增加。这些发现表明,GPX7 的调节作用可能是通过涉及铁死亡的途径介导的。总的来说,本研究揭示了 GPX7 通过部分涉及铁死亡的机制,减轻了 IL-1β诱导的软骨细胞炎症、凋亡和 ECM 降解。本研究的结果为随后的 OA 相关研究奠定了理论基础,并可能为 OA 的治疗开发转化策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ae0/11129537/1dcd520d7d94/mmr-30-01-13242-g00.jpg

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