Yang Qining, Zhou Yongwei, Cai Pengfei, Fu Weicong, Wang Jinhua, Wei Qiang, Li Xiaofei
Department of Joint Surgery, Jinhua Municipal Central Hospital, Jinhua, Zhejiang 321000, People's Republic of China.
Drug Des Devel Ther. 2019 Jul 23;13:2503-2512. doi: 10.2147/DDDT.S211051. eCollection 2019.
Osteoarthritis (OA) is a common joint disease, which is characterized by degradation of articular cartilage. Evidence indicated that miR-23b-3p was upregulated in cartilage tissues of a patient with OA. However, the mechanism by which miR-23b-3p regulates the occurrence and development of OA remains unclear. Thus, this study aimed to investigate the role of miR-23b-3p in the progression of OA.
In this study, qRT-PCR was used to measure the expression of miR-23b-3p in OA tissue samples and normal controls, respectively. Western blotting assay was performed to detect the levels of collagen II, aggrecan, Bax and active caspase 3 in CHON-001 cells. In addition, the dual-luciferase reporter system assay was used to detect the interaction between miR-23b-3p and COL11A2 in OA.
The levels of miR-23b-3p were upregulated, while the expressions of collagen II and aggrecan were decreased in OA tissues and in IL-1β-treated CHON-001 cells. In addition, IL-1β significantly induced apoptosis of CHON-001 cells via increasing the levels of Bax and active caspase 3. However, downregulation of miR-23b-3p markedly inhibited IL-1β-induced apoptosis in CHON-001 cells via increasing the collagen II and aggrecan levels and decreasing Bax and active caspase 3 expressions. Meanwhile, dual-luciferase assay showed that COL11A2 was the direct target of miR-23b-3p in CHON-001 cells. Overexpression of miR-23b-3p markedly decreased the level of COL11A2 in cells. Moreover, downregulation of miR-23b-3p alleviated synovitis/cartilage destruction and reduced Osteoarthritis Research Society International scores and subchondral bone thickness in vivo.
Downregulation of miR-23b-3p could alleviate the progression of OA through upregulating COL11A2 in vivo and in vitro. Therefore, downregulation of miR-23b-3p might be a potential therapeutic strategy for the treatment of OA.
骨关节炎（OA）是一种常见的关节疾病，其特征是关节软骨退变。有证据表明，OA患者软骨组织中miR-23b-3p上调。然而，miR-23b-3p调节OA发生发展的机制仍不清楚。因此，本研究旨在探讨miR-23b-3p在OA进展中的作用。
在本研究中，分别采用qRT-PCR检测OA组织样本和正常对照中miR-23b-3p的表达。进行蛋白质免疫印迹分析以检测CHON-001细胞中Ⅱ型胶原蛋白、聚集蛋白聚糖、Bax和活化的半胱天冬酶3的水平。此外，采用双荧光素酶报告系统检测OA中miR-23b-3p与COL11A2之间的相互作用。
OA组织和IL-1β处理的CHON-001细胞中，miR-23b-3p水平上调，而Ⅱ型胶原蛋白和聚集蛋白聚糖的表达降低。此外，IL-1β通过增加Bax和活化的半胱天冬酶3的水平显著诱导CHON-001细胞凋亡。然而，下调miR-23b-3p可通过增加Ⅱ型胶原蛋白和聚集蛋白聚糖水平以及降低Bax和活化的半胱天冬酶3的表达，显著抑制IL-1β诱导的CHON-001细胞凋亡。同时，双荧光素酶检测表明COL11A2是CHON-001细胞中miR-23b-3p的直接靶点。miR-23b-3p过表达显著降低细胞中COL11A2的水平。此外，下调miR-23b-3p可减轻体内滑膜炎/软骨破坏，并降低国际骨关节炎研究学会评分和软骨下骨厚度。
下调miR-23b-3p可通过在体内和体外上调COL11A2来缓解OA的进展。因此，下调miR-23b-3p可能是治疗OA的一种潜在治疗策略。
