Department of Orthopaedics, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.
Department of Orthopaedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
J Cell Physiol. 2019 Jul;234(7):10523-10534. doi: 10.1002/jcp.27730. Epub 2018 Nov 19.
Osteoarthritis (OA) is the most common disease of arthritis, a chronic joint disease that is always correlated with massive destruction such as cartilage destruction, inflammation of the synovial membrane, and so on. This study aims to explore the role of long noncoding RNA (lncRNA) LOC101928134 in the synovial hyperplasia and cartilage destruction, more specifically, in the Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathway in an OA rat model. Microarray-based gene expression analysis was conducted to screen out the lncRNA differentially expressed in OA and predict the target gene of the lncRNA with the involvement of the signaling pathway through Kyoto encyclopedia of genes and genomes (KEGG) analysis. A model of OA was established and treated with the small interfering RNA LOC101928134/inhibitor of JAK/STAT signaling pathway to investigate the relationship among LOC101928134, IFNA1, and the JAK/STAT signaling pathway in OA. The effect of LOC101928134 on the serum levels of IFNA1, interleukin-1β, and tumor necrosis factor-α, and the apoptosis of synovial and cartilage cells was evaluated. LOC101928134, which was found to be highly expressed in knee joint synovial tissues of OA rats, regulated the expression of IFNA1 gene and inhibited JAK/STAT signaling pathway. Downregulation of LOC101928134 resulted in reduced knee joint synovitis, relived inflammatory damage, and knee joint cartilage damage of OA rats. Besides, synovial cell apoptosis was enhanced upon LOC101928134 downregulation, while cartilage cell apoptosis of OA rats was suppressed. These results demonstrate that downregulation of LOC101928134 suppresses the synovial hyperplasia and cartilage destruction of OA rats via activation of JAK/STAT signaling pathway by upregulating IFNA1, providing a new candidate for the treatment of OA.
骨关节炎（OA）是关节炎中最常见的疾病，是一种慢性关节疾病，总是与大量破坏相关，如软骨破坏、滑膜炎症等。本研究旨在探讨长链非编码 RNA（lncRNA）LOC101928134 在 OA 大鼠模型中的滑膜增生和软骨破坏中的作用，更具体地说，在 Janus 激酶/信号转导和转录激活因子（JAK/STAT）信号通路中的作用。通过基因表达芯片分析筛选出 OA 中差异表达的 lncRNA，并通过京都基因与基因组百科全书（KEGG）分析预测该 lncRNA 参与信号通路的靶基因。建立 OA 模型，并采用 LOC101928134 小干扰 RNA/ JAK/STAT 信号通路抑制剂进行处理，以研究 LOC101928134、IFNA1 和 OA 中的 JAK/STAT 信号通路之间的关系。评估 LOC101928134 对 OA 大鼠血清中 IFNA1、白细胞介素-1β 和肿瘤坏死因子-α 的水平以及滑膜和软骨细胞凋亡的影响。LOC101928134 在 OA 大鼠膝关节滑膜组织中高表达，调节 IFNA1 基因的表达并抑制 JAK/STAT 信号通路。下调 LOC101928134 可减少 OA 大鼠膝关节滑膜炎、减轻炎症损伤和膝关节软骨损伤。此外，下调 LOC101928134 可增强 OA 大鼠滑膜细胞凋亡，抑制软骨细胞凋亡。这些结果表明，下调 LOC101928134 通过上调 IFNA1 激活 JAK/STAT 信号通路，抑制 OA 大鼠的滑膜增生和软骨破坏，为 OA 的治疗提供了一个新的候选药物。
