Chen Hongwei, He Chuan, Liu Yan, Li Xiaolin, Zhang Chaoju, Qin Qunyan, Pang Qixiong
The Third Clinical Medical School, Yangtze University, Jingzhou, Hubei, China.
Department of orthopedics, Jingzhou Traditional Chinese Medicine Hospital, Jingzhou, Hubei, China.
Dose Response. 2020 Dec 9;18(4):1559325820942718. doi: 10.1177/1559325820942718. eCollection 2020 Oct-Dec.
We explored whether long noncoding RNA growth arrest-specific transcript 5 (LncRNA-GAS5) small interfering RNA (siRNA) reduced cartilage destruction in obese mice with adjuvant-induced arthritis. We studied the effects of LncRNA-GAS5 siRNA on the polyarthritis index; hind paw swelling; and the serum levels of certain biochemicals, cytokines, and oxidative stress parameters. We measured the expression levels of matrix metalloproteinases (MMP)-13, NF-κB, fibroblast growth factor (FGF) 21, p38, Akt, and PI3K in cartilage via Western blotting and quantitative reverse transcription PCR. Long noncoding RNA-GAS5 siRNA reduced joint swelling; the serum levels of arthritis-associated biochemicals, cytokines, and oxidative stress markers; and cartilage MMP-13, NF-κB, FGF21, p38, Akt, and PI3K levels. Cartilage miR-103 expression was reduced. Histopathologically, LncRNA-GAS5 siRNA ameliorated the pathological changes of cartilage. Long noncoding RNA-GAS5 siRNA prevented cartilage destruction by inhibiting miR-103 expression.
我们探究了长链非编码RNA生长停滞特异性转录本5(LncRNA-GAS5)小干扰RNA(siRNA)是否能减轻佐剂诱导性关节炎肥胖小鼠的软骨破坏。我们研究了LncRNA-GAS5 siRNA对多关节炎指数、后爪肿胀以及某些生化物质、细胞因子和氧化应激参数血清水平的影响。我们通过蛋白质免疫印迹法和定量逆转录聚合酶链反应检测软骨中基质金属蛋白酶(MMP)-13、核因子κB(NF-κB)、成纤维细胞生长因子(FGF)21、p38、蛋白激酶B(Akt)和磷脂酰肌醇-3激酶(PI3K)的表达水平。LncRNA-GAS5 siRNA减轻了关节肿胀、与关节炎相关的生化物质、细胞因子和氧化应激标志物的血清水平,以及软骨中MMP-13、NF-κB、FGF21、p38、Akt和PI3K的水平。软骨中微小RNA(miR)-103的表达降低。组织病理学检查显示,LncRNA-GAS5 siRNA改善了软骨的病理变化。LncRNA-GAS5 siRNA通过抑制miR-103的表达防止软骨破坏。