聚焦低强度脉冲超声通过恢复受损的 FUNDC1 介导的线粒体自噬来缓解骨关节炎。
Focused low-intensity pulsed ultrasound alleviates osteoarthritis via restoring impaired FUNDC1-mediated mitophagy.
作者信息
Ye Haixia, Li Dongqian, Wei Xia, Yu Lehua, Jia Lang
机构信息
Department of Rehabilitation Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
Department of Rehabilitation Teaching and Research, Chongqing City Management College, Chongqing 401331, China.
出版信息
iScience. 2023 Aug 30;26(10):107772. doi: 10.1016/j.isci.2023.107772. eCollection 2023 Oct 20.
Mitophagy is critical for maintaining proper cellular functions, and it contributes to the onset and progression of osteoarthritis (OA). A recent study showed that focused low-intensity pulsed ultrasound (FLIPUS) could activate mitophagy, but the molecular mechanism remains unclear. This study aimed to elucidate the chondroprotective effects of FLIPUS in OA and the regulatory effects on FUN14-domain containing 1 (FUNDC1-mediated mitophagy. , FLIPUS improved inflammatory response, anabolism, and catabolism in interleukin (IL)-1β-induced OA chondrocytes. The chondroprotective effects of FLIPUS were attributed to promoting the expression of phosphoglycerate mutase 5 (PGAM5) and the dephosphorylation of FUNDC1 at serine 13 (Ser13), as well as promoting the mitophagy process. , FLIPUS reduced the cartilage degeneration and apoptosis and reversed the change of anabolic- and catabolic-related proteins in destabilized medial meniscus (DMM)-induced mouse model. Thus, the study indicates that FLIPUS exhibits a chondroprotective effect via activating impaired FUNDC1-mediated mitophagy.
线粒体自噬对于维持细胞正常功能至关重要，并且它在骨关节炎（OA）的发生和发展中起作用。最近的一项研究表明，聚焦式低强度脉冲超声（FLIPUS）可激活线粒体自噬，但其分子机制仍不清楚。本研究旨在阐明FLIPUS在OA中的软骨保护作用以及对含FUN14结构域蛋白1（FUNDC1）介导的线粒体自噬的调控作用。FLIPUS改善了白细胞介素（IL）-1β诱导的OA软骨细胞中的炎症反应、合成代谢和分解代谢。FLIPUS的软骨保护作用归因于促进磷酸甘油酸变位酶5（PGAM5）的表达以及FUNDC1丝氨酸13（Ser13）位点的去磷酸化，以及促进线粒体自噬过程。在不稳定内侧半月板（DMM）诱导的小鼠模型中，FLIPUS减少了软骨退变和凋亡，并逆转了合成代谢和分解代谢相关蛋白的变化。因此，该研究表明FLIPUS通过激活受损的FUNDC1介导的线粒体自噬发挥软骨保护作用。
Zotero 插件