Circ_0136474 and MMP‐13 suppressed cell proliferation by competitive binding to miR‐127‐5p in osteoarthritis

Abstract

Osteoarthritis (OA) is a prevalent degenerative joint disease whose pathogenesis remains unclear. The research aims to investigate the roles of Circ_0136474/miR‐127‐5p/MMP‐13 axis in OA. Differentially expressed circRNAs and miRNAs in OA cartilage tissue were screened out and visualized by R project based on RNA‐seq data and microarray data respectively. qRT‐PCR was carried out for detection of relative expression levels of Circ_0136474, miR‐127‐5p, MMP‐13 and other inflammatory factors and Western blot analysis was conducted to detect the protein expression level of MMP‐13. CCK‐8 assay and flow cytometry were conducted to determine cell proliferation and cell apoptotic ability respectively. RNA‐fluorescence in situ hybridization (RNA‐FISH) experiments were conducted to confirm the immune‐localization of the Circ_0136474 and MMP‐13 in human tissues. Targeted relationships were predicted by bioinformatic analysis and verified by dual‐luciferase reporter assay. Our findings revealed that the expression levels of both Circ_0136474 and MMP‐13 in OA cartilage tissue were significantly higher than that in normal cartilage tissue. Circ_0136474 could suppress cell proliferation by facilitating MMP‐13 expression and suppressing miR‐127‐5p expression in OA. Overexpression of miR‐127‐5p negatively regulated MMP‐13 expression to enhance cell proliferation. Our study demonstrated that Circ_0136474 and MMP‐13 suppressed cell proliferation, while enhanced cell apoptosis by competitive binding to miR‐127‐5p in OA, which may well provide us with a new therapeutic strategy for osteoarthritis.

LEF1 mediates osteoarthritis progression through circRNF121/miR-665/MYD88 axis via NF-кB signaling pathway

“…Altered expression of circRNA played an important role in the process of OA 29 – 31 . Zhao et al demonstrated that Circ_0136474 and MMP‐13 suppressed cell proliferation, while it enhanced cell apoptosis by competitive binding to miR-127-5p in OA 32 . Four circRNAs associated with RNF121 were selected and analyzed in the current study.…”

Circular RNAs in osteoarthritis: indispensable regulators and novel strategies in clinical implications

“…The expression of circ_0136474 in OA tissue was markedly increased compared with the normal counterpart according to the microarray analysis conducted by Li et al [ 24 ]. Furthermore, cell counting kit-8 (CCK-8) assay, flow cytometry, and dual-luciferase reporter assay illustrated that overexpression of circ_0136474 in OA could inhibit the proliferation and promote the apoptosis of chondrocytes by competitive binding to miR-127-5p [ 24 ]. The immune-localization between circ_0136474 and matrix metalloproteinase 13 (MMP-13), a central regulator in cartilage degradation [ 89 ], has been confirmed by RNA fluorescence in situ hybridization (FISH) assy.…”

“…Recently, the relationship between OA and circRNAs has been partially elucidated. Emerging studies suggested that circRNAs could participate in the development of OA through mechanisms such as interfering chondrocytes proliferation and apoptosis [ 24 ], regulating ECM degradation [ 25 ], and inflammation [ 26 ]. Herein, in this review, we have summarized the roles of circRNAs in OA microenvironment, development, and putative treatment, as well as discussed the future directions toward circRNAs in OA.…”

CircRNA_0092516 regulates chondrocyte proliferation and apoptosis in osteoarthritis through the miR-337-3p/PTEN axis

“…Increasing evidence indicates that the dysregulation of circRNAs is closely related to the progress of various human diseases. For instance, Zhao et al found that circ_0136474 is signi cantly up-regulated in OA cartilage tissues, and this highly expressed circ_0136474 inhibits chondrocyte proliferation and promotes cell apoptosis [8]. Shen et al indicated that the overexpression of circSERPINE2 impedes the progression of OA by inhibiting human chondrocyte apoptosis [9].…”