Circular RNA Atp9b, a competing endogenous RNA, regulates the progression of osteoarthritis by targeting miR-138-5p
| Autor: | Zhi-bin Zhou, Aimin Chen, Lei Zhu, Gao-xiang Huang, Di Du |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Cartilage
Articular 0301 basic medicine Interleukin-1beta Type II collagen Biology Models Biological Chondrocyte Cell Line Extracellular matrix Mice 03 medical and health sciences Chondrocytes Circular RNA Osteoarthritis microRNA Genetics medicine Animals Humans miR-138 Collagen Type II Gene knockdown Binding Sites Competing endogenous RNA RNA Circular General Medicine Extracellular Matrix Up-Regulation Cell biology MicroRNAs 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation Disease Progression RNA |
| Zdroj: | Gene. 646:203-209 |
| ISSN: | 0378-1119 |
| DOI: | 10.1016/j.gene.2017.12.064 |
| Popis: | Osteoarthritis (OA) is the most common joint disease and is mainly characterized by degradation of the articular cartilage. Recently, circular RNAs (circRNAs), novel noncoding RNAs with different biological functions and pathological implications, have been reported to be closely associated with various diseases. Growing evidence indicates that circRNAs act as competing endogenous RNAs (ceRNAs) that bind with microRNAs (miRNAs) and regulate their downstream functions. Here, we identified a new circRNA, circRNA_Atp9b, and further investigated its function in OA using a well-established mouse chondrocyte model. We demonstrated that circRNA_Atp9b expression was significantly up-regulated in mouse chondrocytes after stimulation with interleukin-1 beta (IL-1β), and that knockdown of circRNA_Atp9b promoted the expression of type II collagen while inhibiting the generation of MMP13, COX-2 and IL-6. Moreover, there was a negative correlation between the expression levels of circRNA_Atp9b and microRNA (miR)-138-5p, indicating that miR-138-5p also played a role in IL-1β-induced chondrocytes. Bioinformatics analysis predicted circRNA_Atp9b directly target miR-138-5p, which was validated by dual-luciferase assay. Further functional experiments revealed that down-regulation of miR-138-5p partly reversed the effects of circRNA_Atp9b on extracellular matrix (ECM) catabolism and inflammation. Taken together, these results suggest that circRNA_Atp9b regulates OA progression by modulating ECM catabolism and inflammation in chondrocytes via sponging miR-138-5p. Our findings provide novel insight into the regulatory mechanism of circRNA_Atp9b in OA and may contribute to establishing potential therapeutic strategies. |
| Databáze: | OpenAIRE |
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