Quercetin (QUR) has been shown to ameliorate knee osteoarthritis (KOA), but its precise mechanism remains unclear. This study aimed to determine whether QUR regulates KOA by modulating E2F Transcription Factor 2 (E2F2) and elucidate the underlying mechanism. A rat anterior cruciate ligament model was established to simulate KOA. Molecular expression levels were evaluated using Reverse Transcription Quantitative Real-Time Polymerase Chain Reaction, Western blot, and immunohistochemistry. Cell viability and apoptosis were assessed using cell counting kit-8 assay and flow cytometry, respectively. E2F2 binding to secreted frizzled-related protein 5 (SFRP5) promoter was confirmed through chromatin immunoprecipitation and dual-luciferase reporter assays. Cartilage pathological damage was evaluated using hematoxylin and eosin and safranine-O/fast-green staining. QUR attenuated Interleukin-1beta-induced chondrocyte inflammation, extracellular matrix (ECM) degradation, and cartilage injury by downregulating E2F2 and inactivating the Wnt5a/Dishevelled 2 (Dvl2)/Jun N-terminal kinase (JNK) pathway. E2F2 bound the SFRP5 promoter and inhibited its transcription, whereas SFRP5 overexpression counteracted E2F2-mediated activation of the Wnt5a/Dvl2/JNK pathway. QUR suppresses chondrocyte inflammation and ECM degradation in KOA by downregulating E2F2 and modulating the SFRP5/Wnt5a/Dvl2/JNK pathway. These findings highlight the E2F2/SFRP5/Wnt5a axis as a promising therapeutic target for KOA and support the further development of quercetin as a potential treatment strategy.
Yao et al. (Sun,) studied this question.