Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China; Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, Zhejiang Province, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China; Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
Free Radic Biol Med. 2020 Apr;150:109-119. doi: 10.1016/j.freeradbiomed.2020.02.024. Epub 2020 Feb 24.
Intervertebral disc degeneration (IDD) is a major cause of low back pain (LBP), and effective therapies are still lacking. Previous studies reported that mitochondrial dysfunction contributes to apoptosis, and urolithin A (UA) specifically induces mitophagy. Herein, we aimed to investigate the protective effect of UA-induced mitophagy on tert-butyl hydroperoxide (TBHP)-induced apoptosis in nucleus pulposus (NP) cells in vitro and a rat model of IDD in vivo. Mitochondrial function, apoptosis, and mitophagy were measured in UA-treated NP cells by western blotting and immunofluorescence; the therapeutic effects of UA on IDD were assessed in rats with puncture-induced IDD. The results showed that UA could activate mitophagy in primary NP cells, and UA treatment inhibited TBHP-induced mitochondrial dysfunction and the intrinsic apoptosis pathway. Mechanistically, we revealed that UA promoted mitophagy by activating AMPK signaling in TBHP-induced NP cells. In vivo, UA was shown to effectively alleviate the progression of puncture-induced IDD in rats. Taken together, our results suggest that UA could be a novel and effective therapeutic strategy for IDD.
椎间盘退变（IDD）是导致下腰痛（LBP）的主要原因，但仍缺乏有效的治疗方法。先前的研究表明，线粒体功能障碍导致细胞凋亡，而尿石素 A（UA）特异性诱导自噬。在此，我们旨在研究 UA 诱导的自噬对体外 TBHP 诱导的髓核（NP）细胞凋亡和体内 IDD 大鼠模型的保护作用。通过 Western blot 和免疫荧光法测量 UA 处理的 NP 细胞中的线粒体功能、凋亡和自噬；通过穿刺诱导的 IDD 评估 UA 对 IDD 的治疗效果。结果表明，UA 可激活原代 NP 细胞中的自噬，UA 治疗可抑制 TBHP 诱导的线粒体功能障碍和内在凋亡途径。在机制上，我们揭示 UA 通过激活 TBHP 诱导的 NP 细胞中的 AMPK 信号来促进自噬。在体内，UA 可有效缓解大鼠穿刺诱导的 IDD 的进展。总之，我们的研究结果表明，UA 可能是治疗 IDD 的一种新的有效治疗策略。
