Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, No.1, East Jianshe Road, Zhengzhou, 450000, Henan Province, China.
Hum Cell. 2021 Jan;34(1):60-75. doi: 10.1007/s13577-020-00433-8. Epub 2020 Oct 10.
Osteoarthritis (OA), which is characterized by articular cartilage degeneration, shows a gradually increasing incidence with age. This study explored the molecular mechanism underlying the proliferation and apoptosis of chondrocytes during OA progression. In this study, chondrocytes were isolated from human knee cartilages. The targeted relationship among nuclear enriched abundant transcript 1 (NEAT1), microRNA-543 (miR-543) and PLA2G4A was predicted on TargetScan V7.2 and starBase and validated by performing dual-luciferase reporter assay. High-expressed NEAT1 was detected in OA cartilage and chondrocytes. NEAT1 was negatively correlated with miR-543 and was low-expressed in OA cartilage and PLA2G4A was negatively correlated with miR-543 and was high-expressed in OA cartilage. In OA chondrocytes, the overexpressed NEAT1 inhibited the expressions of p-Akt1 and Bcl-2 and upregulated that of matrix metalloprotease (MMP)-3, MMP-9, MMP-13, interleukin (IL)-6 and IL-8, but such effects of overexpressed NEAT1 were reversed by miR-543 mimic. SiRNA-NEAT1 exerted an opposite effect to NEAT1 overexpression on OA chondrocytes, but this could be reversed by miR-543 inhibitor. The effect of PLA2G4A overexpression was the opposite to miR-543 mimic on OA chondrocytes. In conclusion, NEAT1 could sponge miR-543 to induce PLA2G4A expression, inhibit chondrocyte proliferation and promote apoptosis.
骨关节炎(OA)的特征是关节软骨退化,其发病率随年龄逐渐增加。本研究探讨了 OA 进展过程中软骨细胞增殖和凋亡的分子机制。本研究从人膝关节软骨中分离出软骨细胞。在 TargetScan V7.2 和 starBase 上预测核富集丰富转录物 1(NEAT1)、微小 RNA-543(miR-543)和 PLA2G4A 之间的靶向关系,并通过双荧光素酶报告基因实验进行验证。在 OA 软骨和软骨细胞中检测到高表达的 NEAT1。NEAT1 与 miR-543 呈负相关,在 OA 软骨中低表达,而 PLA2G4A 与 miR-543 呈负相关,在 OA 软骨中高表达。在 OA 软骨细胞中,过表达的 NEAT1 抑制 p-Akt1 和 Bcl-2 的表达,并上调基质金属蛋白酶(MMP)-3、MMP-9、MMP-13、白细胞介素(IL)-6 和 IL-8 的表达,但过表达的 NEAT1 的这种作用可以被 miR-543 模拟物逆转。siRNA-NEAT1 对 OA 软骨细胞的作用与过表达 NEAT1 相反,但可以被 miR-543 抑制剂逆转。过表达 PLA2G4A 对 OA 软骨细胞的作用与 miR-543 模拟物相反。总之,NEAT1 可以海绵 miR-543 诱导 PLA2G4A 表达,抑制软骨细胞增殖并促进凋亡。