Circular RNA circ_0000423 regulates cartilage ECM synthesis via circ_0000423/miRNA-27b-3p/MMP-13 axis in osteoarthritis

Abstract

Circular RNA (circRNA) is related to many human diseases including osteoarthritis (OA). Our research purpose was to show that functional circRNAs have a role in the pathogenesis of OA, while also identifying potential circRNA that bind to miRNA-27b-3p. Microarray analysis was used to evaluate the expression of CircRNA in OA and normal cartilage. The role and functional mechanism of Circ_0000423 up-regulation were detected in OA and verified in vitro and in vivo . RNA transfection, qRT-PCR, Western blot analysis, immunofluorescence, and dual-luciferase assays were used to investigate the interaction between Circ_0000423 and miRNA-27b-3p in vitro . The roles of Circ_0000423 were discussed in vivo . Our results discovered 11 down-regulated circRNAs and 101 up-regulated circRNAs between control and OA tissues, and confirmed that Circ_0000423 an increase significantly in OA tissues by evaluating the different circRNAs expressions. Meanwhile, luciferase analysis confirmed Circ_0000423 can be directly targeted by miRNA-27b-3p and act as a miRNA-27b-3p sponge. Circ_0000423 can influence MMP-13 and collagen II expression by targeting miRNA-27b-3p expression as ceRNA in OA. Furthermore, AAV-shRNA-Circ 0000423 intra-articular injection slows the progression of OA by decreasing articular cartilage destruction and erosion, joint surface fibrosis, osteophyte formation, MMP-13 expression, and increasing collagen II expression in the articular cartilage of ACLT-induced OA mice model. These findings confirmed that the Circ_0000423-miRNA-27b-3p-MMP-13 axis could affect the pathogenesis of OA which might lead to a novel target for diagnostic molecular biological indicators and potential OA treatments.

circRNA-ZCCHC14 affects the chondrogenic differentiation ability of peripheral blood-derived mesenchymal stem cells by regulating GREM1 through miR-181a

“…Multiple studies have found that circRNAs play an important role in OA. For example, circ_0000423 regulates cartilage ECM synthesis through the miRNA-27b-3p/MMP-13 axis 29 . TGF-β1 regulates chondrocyte proliferation and extracellular matrix synthesis in osteoarthritis through the circPhf21a-Vegfa axis 30 .…”

Cartilage Homeostasis and Osteoarthritis

“…Furthermore, 119 upregulated and 136 downregulated circRNAs were identified by RNA-seq in an OA mouse model induced by IL-1β [ 133 ]. A total of 11 downregulated and 101 upregulated circRNAs were identified in OA cartilage [ 134 ]. These changes in circRNA expression patterns indicate a potential function in OA.…”

“…CircADAMTS6/miR-324-5p/PIK3R3 axis participate in IL-1β-induced human chondrocyte dysfunction via the PI3K/AKT/mTOR signaling pathway [ 146 ]. Besides, the circ_0000423/miR-27b-3p/MMP-13 axis can affect the pathogenesis of OA [ 134 ]. Nevertheless, further research on the relationship between circRNAs and OA is required.…”

Identification and comprehensive analysis of circRNA–miRNA–mRNA regulatory networks in osteoarthritis

“…Over the last few decades, the function of circRNAs has become one of the most discussed issues, and circRNAs have been investigated as novel biomarkers of multiple diseases. Accumulated evidence indicates that circRNAs function as a sponge for the miRNAs involved in post-transcriptional regulation in OA ( 29 ). A recent study investigated the circRNA profiles in the osteoarthritic synovium and found that the hsa_circ_0072697–hsa_miR-6736–5p-LEP/ULK1 axis plays a role in cell senescence regulation ( 30 ).…”