Vitexin Alleviates Knee Osteoarthritis-Associated Cartilage Damage Associated with F3 Modulation

Background/Objects: Knee osteoarthritis (KOA) is characterized by pain and progressive cartilage damage, but the underlying molecular mechanisms remain incompletely understood. This study aimed to identify candidate genes through pain-related screening in KOA and explore the potential mechanism by which Vitexin alleviates cartilage damage.

Transcriptomic analysis was performed on peripheral blood samples from control and KOA model mice, and differentially expressed genes were intersected with pain-related genes to identify candidate targets. GO enrichment analysis was subsequently performed to explore their potential biological functions. The role of F3 in KOA was further investigated in vivo using F3-targeting siRNA, followed by VEGFA rescue experiments to evaluate its association with CD31-positive vascular changes. Safranin O/Fast Green staining and immunofluorescence staining for F3, CD31, and COL2A1 were used to assess cartilage damage and angiogenesis. Finally, Vitexin was administered to KOA mice to investigate its potential effects on F3-associated pathological changes.

Integration of transcriptomic data with pain-related genes identified F3 and F8 as candidate genes in KOA. Exploratory GO analysis indicated that F3 was annotated to several angiogenesis-related biological processes. F3 protein expression was markedly increased in the tibial plateau of KOA mice. F3 knockdown reduced CD31 expression, restored COL2A1 expression and cartilage proteoglycan content, and attenuated cartilage damage. VEGFA administration reversed the F3 knockdown-induced reduction in CD31-positive vascular signals and the associated improvement in cartilage damage without restoring F3 expression, suggesting that vascular changes may represent a downstream process associated with F3. Furthermore, Vitexin treatment reduced F3 and CD31 expression, partially restored COL2A1 expression, and alleviated cartilage proteoglycan loss in KOA mice.

F3 may contribute to KOA-associated cartilage damage by promoting pathological angiogenesis. Vitexin treatment reduced F3 expression and CD31-positive vascular signals, accompanied by alleviation of cartilage damage. These findings identify F3 as a candidate derived from pain-related gene screening and suggest its potential involvement in pathological angiogenesis and cartilage damage in KOA.