Department of Orthopedics, Medical School of Chinese PLA, Beijing, China.
Department of Orthopedics, The Fourth Comprehensive Service and Support Center of the PLA Beijing Administration of Veterans Service Affairs, Beijing, China.
Pathol Int. 2020 Mar;70(3):155-165. doi: 10.1111/pin.12875. Epub 2020 Feb 9.
Previous studies demonstrated that dysregulation of G protein-coupled receptor 120 (GPR120) plays a protective role in osteoarthritis (OA). However, the mechanism underlying how GPR120 is downregulated remains largely unknown. In the present study, we evaluated whether GPR120 is regulated by microRNAs (miRNAs) and long noncoding RNAs (lncRNAs). Our results show that GPR120 was negatively regulated by miR-15b-5p through targeting 3' untranslated region (3'UTR), and that miR-15b-5p was negatively regulated by LINC00662. Further luciferase assay shows that LINC00662-miR-15b-5p signaling pathway contributed the regulation of GPR120 expression. Functionally, the decreased of LINC00662 caused increased miR-15b-5p, thereby leading to decreased GPR120. The decreased GPR120 then contributes to increased expression of inflammatory factors including tumor necrosis factor α (TNF-α), interleukin (IL)-6 and IL-8, cell apoptosis, and decreased apoptosis-related protein levels including cleaved caspase-3, cleaved caspase-9, and Bax in cultured rat chondrocytes. In summary, the present study shows that LINC00662-miR-15b-5p signaling pathway is involved in the regulation of GPR120, thereby contributing to arthritis.
先前的研究表明，G 蛋白偶联受体 120（GPR120）的失调在骨关节炎（OA）中发挥保护作用。然而，GPR120 下调的机制在很大程度上尚不清楚。在本研究中，我们评估了 GPR120 是否受 microRNAs（miRNAs）和长链非编码 RNA（lncRNAs）的调节。我们的结果表明，GPR120 被 miR-15b-5p 通过靶向 3'非翻译区（3'UTR）负调控，miR-15b-5p 被 LINC00662 负调控。进一步的荧光素酶报告基因实验表明，LINC00662-miR-15b-5p 信号通路参与 GPR120 表达的调控。功能上，LINC00662 的减少导致 miR-15b-5p 的增加，从而导致 GPR120 的减少。减少的 GPR120 继而导致炎症因子（包括肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-6 和 IL-8）的表达增加，细胞凋亡增加，以及培养的大鼠软骨细胞中凋亡相关蛋白（包括 cleaved caspase-3、cleaved caspase-9 和 Bax）水平降低。总之，本研究表明，LINC00662-miR-15b-5p 信号通路参与 GPR120 的调节，从而促进关节炎的发生。
