Foot Ankle Center, The Xi'an Honghui Hospital, Xi'an 710054, Shaanxi, China.
Department of Urology Surgery, The Xi'an Honghui Hospital, Xi'an 710054, Shaanxi, China.
Int Immunopharmacol. 2021 Jan;90:107150. doi: 10.1016/j.intimp.2020.107150. Epub 2020 Dec 6.
As a common joint disease, osteoarthritis (OA) is the main cause of limited joint mobility and disability. The role of lncRNAs in the regulation of OA is increasingly discovered. Therefore, further exploring the function of SNHG7 in OA is of great significance for understanding its occurrence and development.
We used interleukin-1β (IL-1β) to treat to establish an OA model primary on chondrocytes in vitro, and gain- and loss of function assays of SNHG7 and miR-214-5p were conducted. The cell viability and apoptosis of chondrocytes were detected by CCK8 assay, BrdU assay and flow cytometry. The inflammatory cytokines (IL-1β, IL-6 and TNF-α), NLRP3 inflammasome, protein level of PPARGC1B, PPARγ, P38 and NF-κB were determined by RT-PCR and/or western blot.
The results showed that SNHG7 was distinctly downregulated, while miR-214-5p was significantly upregulated in OA patients and primary chondrocytes treated with IL-1β. In addition, SNHG7 enhanced cell viability, inhibited apoptosis and inflammation of IL-1β-mediated chondrocytes. In contrast, miR-214-5p upregulation reduced viability, promoted apoptosis and inflammation of chondrocytes. Mechanistically, SNHG7 served as a competitive endogenous RNA by sponging miR-214-5p, which targeted PPARGC1B. Besides, the results of the compensation experiment affirmed that miR-214-5p attenuates SNHG7-mediated protective effects on IL-1β-mediated chondrocytes against apoptosis and inflammation, and activating PPARγ pathway markedly dampened the cytotoxic effects of miR-214-5p.
Collectively, The above results confirmed that SNHG7 prevents IL-1β induced OA by inhibiting NLRP3 inflammasome and apoptosis through miR-214-5p/PPARGC1B axis.
骨关节炎（OA）作为一种常见的关节疾病，是导致关节活动度受限和残疾的主要原因。lncRNAs 在 OA 中的调控作用日益被发现。因此，进一步探讨 SNHG7 在 OA 中的作用对于了解其发生发展具有重要意义。
我们使用白细胞介素-1β（IL-1β）在体外处理原代软骨细胞建立 OA 模型，并进行 SNHG7 和 miR-214-5p 的功能获得和功能丧失实验。通过 CCK8 法、BrdU 法和流式细胞术检测软骨细胞的活力和凋亡。通过 RT-PCR 和/或 Western blot 检测炎性细胞因子（IL-1β、IL-6 和 TNF-α）、NLRP3 炎性小体、PPARGC1B、PPARγ、P38 和 NF-κB 蛋白水平。
结果表明，OA 患者和 IL-1β 处理的原代软骨细胞中 SNHG7 明显下调，而 miR-214-5p 明显上调。此外，SNHG7 增强了 IL-1β 介导的软骨细胞的活力，抑制了凋亡和炎症。相反，miR-214-5p 的上调降低了软骨细胞的活力，促进了其凋亡和炎症。机制上，SNHG7 通过海绵吸附 miR-214-5p 作为竞争性内源性 RNA，靶向 PPARGC1B。此外，补偿实验的结果证实，miR-214-5p 减弱了 SNHG7 对 IL-1β 介导的软骨细胞抗凋亡和抗炎作用，激活 PPARγ 通路显著减弱了 miR-214-5p 的细胞毒性作用。
综上所述，上述结果证实，SNHG7 通过 miR-214-5p/PPARGC1B 轴抑制 NLRP3 炎性小体和凋亡来防止 IL-1β 诱导的 OA。
