Department of Orthopedics, Shenzhen Hospital of Southern Medical University, Shenzhen, Guangdong 518101, P.R. China.
Department of Orthopedics, The Second People's Hospital of Huai'an, Huai'an, Jiangsu 223002, P.R. China.
Mol Med Rep. 2021 Apr;23(4). doi: 10.3892/mmr.2021.11892. Epub 2021 Feb 4.
As a chronic degenerative joint disease, the characteristics of osteoarthritis (OA) are degeneration of articular cartilage, subchondral bone sclerosis and bone hyperplasia. It has been reported that microRNA (miR)‑186‑5p serves a key role in the development of various tumors, such as osteosarcoma, non‑small‑cell lung cancer cells, glioma and colorectal cancer. The present study aimed to investigate the effect of miR‑186‑5p in OA. Different concentrations of IL‑1β were used to treat the human chondrocyte cell line CHON‑001 to simulate inflammation, and CHON‑001 cell injury was assessed by detecting cell viability, apoptosis, caspase-3 activity and the levels of TNF‑α, IL‑8 and IL‑6. Subsequently, reverse transcription‑quantitative PCR was performed to measure miR‑186‑5p expression. The results demonstrated that following IL‑1β treatment, CHON‑001 cell viability was suppressed, apoptosis was promoted, the caspase-3 activity was significantly enhanced and the release of TNF‑α, IL‑8 and IL‑6 was increased. In addition, IL‑1β treatment significantly upregulated miR‑186‑5p expression in CHON‑001 cells. It was also identified that MAPK1 was a target gene of miR‑186‑5p, and was negatively regulated by miR‑186‑5p. miR‑186 inhibitor and MAPK1‑small interfering RNA (siRNA) were transfected into CHON‑001 cells to investigate the effect of miR‑186‑5p on CHON‑001 cell injury induced by IL‑1β. The results demonstrated that miR‑186 inhibitor suppressed the effects of IL‑1β on CHON‑001 cells, and these effects were reversed by MAPK1‑siRNA. In conclusion, the present results indicated that miR‑186‑5p could attenuate IL‑1β‑induced chondrocyte inflammation damage by increasing MAPK1 expression, suggesting that miR‑186‑5p may be used as a potential therapeutic target for OA.
作为一种慢性退行性关节疾病，骨关节炎（OA）的特征是关节软骨退化、软骨下骨硬化和骨质增生。据报道，微小 RNA（miR）-186-5p 在多种肿瘤的发展中发挥着关键作用，如骨肉瘤、非小细胞肺癌细胞、神经胶质瘤和结直肠癌。本研究旨在探讨 miR-186-5p 在 OA 中的作用。使用不同浓度的白细胞介素-1β（IL-1β）处理人软骨细胞系 CHON-001 以模拟炎症，并通过检测细胞活力、细胞凋亡、半胱天冬酶-3 活性以及肿瘤坏死因子-α（TNF-α）、白细胞介素-8（IL-8）和白细胞介素-6（IL-6）的水平来评估 CHON-001 细胞损伤。随后，进行逆转录-定量聚合酶链反应以测量 miR-186-5p 的表达。结果表明，在 IL-1β 处理后，CHON-001 细胞活力受到抑制，细胞凋亡增加，半胱天冬酶-3 活性显著增强，TNF-α、IL-8 和 IL-6 的释放增加。此外，IL-1β 处理显著上调了 CHON-001 细胞中 miR-186-5p 的表达。还确定 MAPK1 是 miR-186-5p 的靶基因，并受 miR-186-5p 的负调控。将 miR-186 抑制剂和 MAPK1-小干扰 RNA（siRNA）转染到 CHON-001 细胞中，以研究 miR-186-5p 对 IL-1β 诱导的 CHON-001 细胞损伤的影响。结果表明，miR-186 抑制剂抑制了 IL-1β 对 CHON-001 细胞的作用，而这些作用被 MAPK1-siRNA 逆转。综上所述，本研究结果表明，miR-186-5p 通过增加 MAPK1 表达来减轻 IL-1β 诱导的软骨细胞炎症损伤，提示 miR-186-5p 可能作为 OA 的潜在治疗靶点。
