Department of Orthopedics, the Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen 528406, China; Department of Spine Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou 510120, China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
Department of Spine Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou 510120, China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
Cell Signal. 2023 Jul;107:110678. doi: 10.1016/j.cellsig.2023.110678. Epub 2023 Apr 14.
Intervertebral disc degeneration (IDD) is associated with low back pain, yet its inherent mechanism remains obscure. Hypercholesteremia was regarded as a risk factor for IDD, and our previous study showed that cholesterol accumulation could elicit matrix degradation in the nucleus pulposus (NP). MicroRNA-155 (miR-155) was substantiated as protective in IDD, but its role in cholesterol-induced IDD was unclear. The present study investigated whether miR-155 could mediate cholesterol-related IDD and its internal mechanisms. In vivo experiments revealed high-fat diet-induced hypercholesteremia in wild-type (WT) mice along with the occurrence of IDD, whereas Rm155LG transgenic mice showed milder NP degeneration, as evidenced by Saffron O-fast green (SF) staining and immunohistochemistry (IHC). Meanwhile, IHC showed that NLRP3 and Bax expression was also suppressed in Rm155LG mice. In vitro studies using Western blotting (WB) and immunofluorescence (IF) confirmed that the miR-155 mimic could alleviate cholesterol-induced matrix degradation, apoptosis and pyroptosis in NP. Moreover, RORα was upregulated in severely degenerated NP compared to mild IDD. It was also noted that RORα was suppressed in Rm155LG mice. In this study, we demonstrated that miR-155 could target RORα and that inhibition of RORα could prevent cholesterol-induced matrix degradation, apoptosis, and pyroptosis in NP, indicating the protective effect of miR-155 in cholesterol-induced IDD by targeting RORα.
椎间盘退行性变（IDD）与下腰痛有关，但其内在机制尚不清楚。高胆固醇血症被认为是 IDD 的危险因素，我们之前的研究表明胆固醇积累可引起髓核（NP）基质降解。MicroRNA-155（miR-155）在 IDD 中被证实具有保护作用，但它在胆固醇诱导的 IDD 中的作用尚不清楚。本研究探讨了 miR-155 是否可以介导胆固醇相关的 IDD 及其内在机制。体内实验显示，高脂饮食诱导野生型（WT）小鼠发生高胆固醇血症和 IDD，而 Rm155LG 转基因小鼠 NP 退变较轻，这可通过藏红花 O-快速绿（SF）染色和免疫组织化学（IHC）证实。同时，IHC 显示 NLRP3 和 Bax 的表达在 Rm155LG 小鼠中也受到抑制。Western blot（WB）和免疫荧光（IF）的体外研究证实，miR-155 模拟物可减轻 NP 中胆固醇诱导的基质降解、细胞凋亡和细胞焦亡。此外，与轻度 IDD 相比，严重退变的 NP 中 RORα 上调。还注意到 RORα 在 Rm155LG 小鼠中受到抑制。在这项研究中，我们证明了 miR-155 可以靶向 RORα，并且抑制 RORα 可以防止 NP 中胆固醇诱导的基质降解、细胞凋亡和细胞焦亡，这表明 miR-155 通过靶向 RORα 在胆固醇诱导的 IDD 中发挥保护作用。
