Molecular mechanism of resveratrol regulating pyroptosis to improve osteoarthritis through transcriptome sequencing and vitro experiments

Background In orthopedics, osteoarthritis (OA) is a prevalent joint damage condition. Pyroptosis is a modifiable cell death that relies on Gasdermin family proteins to create plasma membrane holes. One potential therapy approach for OA is to modulate pyroptosis proteins and inhibit the expression of inflammatory cytokines. Many researches have found that resveratrol can improve OA, but the molecular mechanism is still unclear. Method Using bioinformatics to find the pyroptosis proteins that are expressed in OA. The TCM database was used to extract the resveratrol proteins, and the intersection was used to determine the resveratrol therapeutic proteins for OA. Molecular docking was used to validate the results. Lastly, the invasion of immune cells was investigated. CCK-8 was used to determine the intervention concentration of resveratrol, protein detection, Q-PCR detection, and immunofluorescence assay was used to examine key proteins and genes. Results In OA, 14 pyroptosis proteins with differential expression were found. IL1β, IL6, and NLRP3 were further identified as significant hub genes. Furthermore, GSDMD, and CASP3 were found to be involved in the regulation of pyroptosis. CCK8 indicates that 10 μ mol/L resveratrol is the optimal intervention concentration for 24 h. Further cell experiments revealed that after intervention with resveratrol, the expression of pyroptosis and inflammation related proteins and genes was recovered. Among them, immunofluorescence assay once again confirmed that the key protein NLRP3 of pyroptosis was regulated in fluorescence intensity. Conclusion We showed that resveratrol attenuates OA via modulating apoptosis, pyroptosis, and immunological processes, these findings may offer a fresh approach to treating OA.