Department of Radiology, The First Hospital of Jilin University, Changchun, People's Republic of China.
Jilin Province Population Life Science and Technology Research Institute, Changchun, People's Republic of China.
IUBMB Life. 2019 Sep;71(9):1355-1366. doi: 10.1002/iub.2050. Epub 2019 Apr 29.
Osteoarthritis (OA) is a degenerative joint disease characterized by joint pain, stiffness, and function degeneration with high incidence. Recent studies have been inspired based on the association between microRNAs (miRs) and therapeutic research of OA. Hence, the present study evaluates the effects of miR-138 on chondrocyte proliferation, differentiation, and apoptosis through the WNT/β-catenin signaling pathway in mice with OA by binding to NIMA-related kinase 2 (NEK2). Appropriate dataset was selected from the Gene Expression Omnibus database, and differentially expressed genes and potential miRNAs that could regulate NEK2 were explored. A mouse model of OA was established. The expressions of miR-138, NEK2, β-catenin, GSK3β, Bcl-2, Bcl-2-associated X protein (Bax), p53, MMP-13, Col2, and Aggrecan and the phosphorylation levels of β-catenin were determined by the reverse transcription quantitative polymerase chain reaction and Western blot analysis. The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and flow cytometry were employed to detect cell proliferation and apoptosis, respectively. The potential functional role of NEK2 was revealed to be related to the WNT/β-catenin signaling pathway, and miR-138 was the putative regulator of NEK2. miR-138 expression was downregulated while expressions of NEK2 and β-catenin as well as the phosphorylation levels of β-catenin were upregulated in mice with OA. The chondrocytes treated with miR-138 mimic and siRNA-NEK2 exhibited reduced expressions of NEK2, β-catenin, MMP-13, Bax, and p53 and elevated expressions of Col2, Aggrecan, and Bcl-2 as well as phosphorylation levels of β-catenin along with enhanced chondrocytes' proliferation and suppressed cell apoptosis. Overexpression of miR-138 induces cell survival and reduces WNT/β-catenin signaling of OA chondrocytes through NEK2. © 2019 IUBMB Life, 71(9):1355-1366, 2019.
骨关节炎（OA）是一种退行性关节疾病，其特征为关节疼痛、僵硬和功能退化，发病率高。最近的研究基于 microRNAs（miRs）与 OA 治疗研究之间的关联得到启发。因此，本研究通过结合 NIMA 相关激酶 2（NEK2）评估了 miR-138 对 OA 小鼠软骨细胞增殖、分化和凋亡的影响及其对 WNT/β-catenin 信号通路的影响。从基因表达综合数据库中选择了合适的数据集，并探索了可能调节 NEK2 的差异表达基因和潜在 miRNAs。建立了 OA 小鼠模型。通过逆转录定量聚合酶链反应和 Western blot 分析测定 miR-138、NEK2、β-catenin、GSK3β、Bcl-2、Bcl-2 相关 X 蛋白（Bax）、p53、MMP-13、Col2 和 Aggrecan 的表达以及β-catenin 的磷酸化水平。采用 3-(4,5-二甲基-2-噻唑基)-2,5-二苯基-2H-四唑溴盐（MTT）法和流式细胞术分别检测细胞增殖和凋亡。揭示了 NEK2 的潜在功能作用与 WNT/β-catenin 信号通路有关，miR-138 是 NEK2 的假定调节因子。OA 小鼠 miR-138 表达下调，NEK2 和β-catenin 表达以及β-catenin 的磷酸化水平上调。miR-138 模拟物和 siRNA-NEK2 处理的软骨细胞显示 NEK2、β-catenin、MMP-13、Bax 和 p53 的表达下调，Col2、Aggrecan 和 Bcl-2 的表达上调以及β-catenin 的磷酸化水平升高，同时增强了软骨细胞的增殖，抑制了细胞凋亡。miR-138 的过表达通过 NEK2 诱导 OA 软骨细胞的细胞存活并降低 WNT/β-catenin 信号。© 2019 IUBMB Life，71（9）：1355-1366，2019。
