Downregulation of Circ_006893 attenuates ferroptosis of osteoarthritis by miR-214-3p/ATF3 signaling

Ferroptosis, a type of programmed cell death distinct from apoptosis and autophagy, is involved in the progression of several diseases. Circular RNAs (circRNAs) can exert critical roles in osteoarthritis (OA). However, the roles of circRNAs in OA remains unclear. In this study, OA rat models were constructed using anterior cruciate ligament transection (ACLT). After extraction of cartilage tissues, differentially expressed RNAs (DE-RNAs) were identified by comparing the expression profiles of mRNAs, microRNAs (miRNAs) and circRNAs with whole transcriptome sequencing (WTS) in OA rats. In vitro cell models of OA were established using IL-1B-treated rat chondrocytes. Circ_006893 was detected for its subcellular localization in chondrocytes using fluorescence in situ hybridization (FISH). Circ_006893 expression was knocked down using lentiviral transduction. Cell viability and proliferation were detected using cell counting kit-8 (CCK-8) assay and 5-ethynyl-2-deoxyuridine (Edu) assay, respectively, apoptosis was detected using flow cytometry, protein expression levels of Bcl-2, Caspase-3, aggrecan and MMP13, as well as inflammation-related factors, were determined using western blot (WB). Dual luciferase gene reporter assay verified that circ-PSEN1 could competitively bind miR-200b-3p to regulate the expression of target gene ATF3. In addition, overexpression of miR-214-3p could inhibit chondrocyte proliferation, and ATF3 could increase the susceptibility to IL-1B-induced chondrocyte ferroptosis.