Trauma Center, General Hospital of Western Theater Command, People's Liberation Army, Chengdu, China.
Department of Pain Treatment, General Hospital of Western Theater Command, People's Liberation Army, Chengdu, China.
Cartilage. 2024 Dec;15(4):428-439. doi: 10.1177/19476035231194771. Epub 2023 Aug 31.
The superficial zone cells in articular cartilage (SFZCs) have been identified as stem/progenitor chondrocytes and promoted cell self-renewal in the osteoarthritis (OA). Several studies emphasized the involvement of senescence and autophagy in OA. Interleukin-1β (IL-1β) is one of the main inflammatory mediators of OA, and whether it induces senescence and autophagy in SFZCs remains unclear. The present study aimed to investigate autophagy flux, mitochondrial function, and intracellular reactive oxygen species (ROS) that resulted in senescence in SFZCs induced by IL-1β.
Using western blotting, reverse transcription-quantitative PCR, immunofluorescence, intracellular ROS detection, mitochondrial staining, and determination of mitochondrial membrane potential, we tested senescence and autophagy markers in SFZCs induced by IL-1β . The consequences of mitochondrial function and ROS were also studied with IL-1β-induced senescence.
IL-1β treatment decreased SFZC proliferation, induced SFZC senescence, and reduced SFZCs' chondrogenic differentiation capacity. Moreover, IL-1β impaired autophagy flux, and the autophagy activator, rapamycin, attenuated the senescence of SFZCs. IL-1β-induced autophagy defect resulted in mitochondrial dysfunction and overproduction of ROS, and autophagy activation notably protected against mitochondrial dysfunction and reduced the levels of ROS. Moreover, antioxidant N-acetylcysteine reversed the senescence of IL-1β in SFZCs.
IL-1β promotes autophagy impairment and subsequently results in dysfunctional mitochondria and overproduction of ROS, which finally causes SFZC senescence.
关节软骨的表层区细胞（SFZCs）已被鉴定为干细胞/祖细胞软骨细胞，并促进了骨关节炎（OA）中的细胞自我更新。有几项研究强调了衰老和自噬在 OA 中的作用。白细胞介素 1β（IL-1β）是 OA 的主要炎症介质之一，但其是否会诱导 SFZCs 衰老和自噬尚不清楚。本研究旨在探讨 IL-1β诱导 SFZCs 衰老过程中的自噬流、线粒体功能和细胞内活性氧（ROS）。
使用 Western blot、逆转录定量 PCR、免疫荧光、细胞内 ROS 检测、线粒体染色和线粒体膜电位测定，检测 IL-1β诱导的 SFZCs 中的衰老和自噬标志物。还研究了线粒体功能和 ROS 的后果与 IL-1β诱导的衰老。
IL-1β处理可降低 SFZC 的增殖能力，诱导 SFZC 衰老，并降低 SFZCs 的软骨分化能力。此外，IL-1β可损害自噬流，而自噬激活剂雷帕霉素可减轻 SFZCs 的衰老。IL-1β诱导的自噬缺陷导致线粒体功能障碍和 ROS 产生增加，而自噬激活可明显保护线粒体功能障碍并降低 ROS 水平。此外，抗氧化剂 N-乙酰半胱氨酸可逆转 SFZCs 中 IL-1β诱导的衰老。
IL-1β促进自噬损伤，进而导致线粒体功能障碍和 ROS 产生增加，最终导致 SFZC 衰老。
