Department of Trauma and Orthopedics, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
Department of Traumatic Orthopedics, Weifang People's Hospital, Weifang, Shandong 261000, P.R. China.
Mol Med Rep. 2020 Mar;21(3):1077-1088. doi: 10.3892/mmr.2020.10940. Epub 2020 Jan 14.
Osteoarthritis (OA) is a degenerative joint disease that affects the physical, and mental health of middle‑aged and elderly people. The aims of the present study were to determine the biological function and molecular mechanisms of miR‑363‑3p in chondrocyte apoptosis. Exploration of the molecular mechanisms of OA may be helpful in the understand of the causes, and facilitating the prevention and treatment of OA. In the present study, the expression of nuclear respiratory factor1 (NRF1) was downregulated in the articular cartilage of OA rats in vivo and lipopolysaccharide (LPS)‑treated chondrocytes in vitro. MicroRNAs (miRNA) are regulators of gene expression in the progression of OA. TargetScan software was used to predict that NRF1 was a potential target for miRNA (miR)‑363, and this was confirmed in subsequent experiments. The expression of miR‑363‑3p was negatively correlated with the expression of NRF1, and its expression was significantly upregulated in OA model rats and in LPS‑induced chondrocytes compared with the expression in the respective controls. In addition, the overexpression of miR‑363‑3p increased the levels of interleukin (IL)‑1β, IL‑6 and tumor necrosis factor‑α in vivo, and was demonstrated to promote chondrocyte injury and apoptosis by Safranin O staining and TUNEL. Moreover, the inhibition of miR‑363‑3p expression increased the expression of NRF1 and protected chondrocytes from apoptosis in vitro and in vivo, whereas the overexpression of miR‑363‑3p downregulated NRF1 expression and promoted LPS‑induced chondrocyte apoptosis through the p53 pathway in vitro. The results of this study suggested that miR‑363‑3p‑mediated inhibition of NRF1may be associated with chondrocyte apoptosis in OA.
骨关节炎（OA）是一种退行性关节疾病，影响中老年人的身心健康。本研究旨在确定 miR-363-3p 在软骨细胞凋亡中的生物学功能和分子机制。探索 OA 的分子机制可能有助于了解其病因，并促进 OA 的预防和治疗。在本研究中，体内 OA 大鼠关节软骨和体外脂多糖（LPS）处理的软骨细胞中核呼吸因子 1（NRF1）的表达下调。microRNAs（miRNA）是 OA 进展中基因表达的调节剂。TargetScan 软件用于预测 NRF1 是 miRNA（miR）-363 的潜在靶标，随后的实验证实了这一点。miR-363-3p 的表达与 NRF1 的表达呈负相关，与各自对照相比，OA 模型大鼠和 LPS 诱导的软骨细胞中 miR-363-3p 的表达显著上调。此外，miR-363-3p 的过表达增加了体内 IL-1β、IL-6 和肿瘤坏死因子-α 的水平，并通过番红 O 染色和 TUNEL 证实促进软骨细胞损伤和凋亡。此外，抑制 miR-363-3p 的表达增加了 NRF1 的表达，并在体外和体内保护软骨细胞免受凋亡，而 miR-363-3p 的过表达通过 p53 途径下调 NRF1 的表达并促进 LPS 诱导的软骨细胞凋亡。这项研究的结果表明，miR-363-3p 介导的 NRF1 抑制可能与 OA 中的软骨细胞凋亡有关。
