Background Osteoarthritis (OA), mainly caused by severe joint degeneration, is often accompanied by joint pain and dysfunction syndrome. Inflammatory mediators and apoptosis play key roles in the evolution of OA. It is reported that daphnoretin has significant antiviral and anti-tumor values. The present study aims at investigating the role of daphnoretin in OA. Methods The OA mouse model was constructed by performing the destabilization of the medial meniscus through surgery, and the OA cell model was induced in ATDC5 chondrocytes with IL-1β (10 ng/mL) in vitro. Chondrocyte viability and apoptosis were measured by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT), Caspase-3 activity, and flow cytometry. The levels of COX-2, iNOS, TNF-α, IL-6, Bax, Bcl2, cleaved-Caspase3, endoplasmic reticulum stress (ERS) proteins (GRP78, CHOP, ATF6, and Caspase-12), and NLRP3-ASC-Caspase1 inflammasome were determined by quantitative real-time PCR or western blot. The concentrations of TNF-α, IL-6, and PGE2 were tested by enzyme-linked immunosorbent assay. The content of nitrates was detected by the Griess method. In vivo, morphologic differences in knee joint sections and the thickness of the subchondral bone density plate in mice were observed by hematoxylin–eosin (H&E) staining and safranin O-fast green staining. Results Daphnoretin effectively choked IL-1β-induced chondrocyte apoptosis and facilitated cell viability. Daphnoretin dose-dependently abated ERS, inflammatory mediators, and the activation of NLRP3 inflammasomes in IL-1β-induced chondrocytes. What’s more, in vivo experiments confirmed that daphnoretin alleviated OA progression in a murine OA model by mitigating inflammation and ERS. Conclusion Daphnoretin alleviated IL-1β-induced chondrocyte apoptosis by hindering ERS and NLRP3 inflammasome. Graphical abstract

Objective Circular RNAs (circRNAs) play important roles in modulating tumour progression. This study investigated the role of circ_0000253 in osteosarcoma (OS). Methods We downloaded the chip dataset GSE140256 from the Gene Expression Omnibus database and the circRNAs differentially expressed in OS tissue and normal tissue samples were analysed. Quantitative real-time PCR (qRT-PCR) was carried out to examine circ_0000253 expression in OS tissues and cells. Cell counting kit-8, BrdU and flow cytometry assays were performed to verify the effects of circ_0000253 on OS cell growth and apoptosis. Bioinformatics analysis was conducted to predict, and RNA immunoprecipitation assay and dual-luciferase reporter gene assay were performed to verify the targeted relationships of miR-1236-3p with circ_0000253 and Sp1 transcription factor (SP1) mRNA 3ʹUTR. The effects of miR-1236-3p and circ_0000253 on SP1 expression in OS cells were detected through Western blot. Key findings Circ_0000253 was upregulated in OS tissues and cell lines. Circ_0000253 overexpression facilitated OS cell growth and suppressed apoptosis, whereas knocking down circ_0000253 inhibited OS cell growth and facilitated apoptosis. Circ_0000253 targeted miR-1236-3p directly and negatively modulated its expression. SP1 was miR-1236-3p’s target gene and positively regulated by circ_0000253. Conclusion Circ_0000253 promotes OS cell proliferation and suppresses cell apoptosis via regulating the miR-1236-3p/SP1 molecular axis.