Long noncoding RNA LINC00662‐miR‐15b‐5p mediated GPR120 dysregulation contributes to osteoarthritis

Abstract

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.

MicroRNAs Involved in the Therapeutic Functions of Noni (Morinda citrifolia L.) Fruit Juice in the Treatment of Acute Gouty Arthritis in Mice Induced with Monosodium Urate

“…Studies have shown that two miRNAs (i.e., mir-30a-5p and miR-15b-5p) are involved in osteoarthritis by combining with two long noncoding RNAs (i.e., LINC00461 and LINC00662) to increase the inflammation and three types of cytokines (i.e., IL-6, IL-8, and TNF-α), respectively [ 25 , 29 , 81 ]. These results were consistent with the findings revealed in our study based on the KEGG enrichment analysis, showing that these two miRNAs were responsive to the treatments of noni fruit juice and colchicine with up- and downregulated expressions in model mice and mice treated with both noni fruit juice and colchicine, respectively ( Table 5 ).…”

“…For example, as one of the important proinflammatory cytokines strongly associated with the inflammation of gout, the IL-1β has been identified as the target of several miRNAs [ 19 , 20 , 21 , 22 , 23 , 24 ], though the regulatory roles of these miRNAs still need to be experimentally verified in vivo [ 25 ]. As another proinflammatory cytokine, the TNF-α has been regulated by various types of miRNAs involved in several signaling pathways [ 19 , 22 , 23 , 24 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ].…”

Interactions Among lncRNA/circRNA, miRNA, and mRNA in Musculoskeletal Degenerative Diseases

“…HOTAIR was involved in the process of apoptosis and ECM degradation by sponging miR-20b and regulating the downstream target PTEN. Lu and Zhou (2020) revealed that lncRNA00662 was downregulated in the cartilage of OA rats. The expression of miR-15b-5p was negative with lncRNA00662, whereas the expression of GPR120 was positively correlated with lncRNA00662.…”

G Protein-Coupled Receptors in Osteoarthritis: A Novel Perspective on Pathogenesis and Treatment

“…In general, GPR120 is involved in the pathogenesis of OA by controlling the inflammatory response, metabolic homeostasis, and osteoclast differentiation. Therefore, the increase in miR-15b-5p caused by the downregulation of LINC00662 is able to downregulate the expression of GPR120, thereby promoting the progression of OA ( Lu and Zhou, 2020 ). In conclusion, some receptors of the GPCR family have a critical effect on the occurrence and progression of OA by regulating the destruction of the cartilage matrix, subchondral bone remodeling, inflammation, and chondrocyte autophagy.…”