The Therapeutic Role of Hyperoside in Medial Meniscus Destabilization-Induced Osteoarthritis: A Study on Subchondral Bone Remodeling

Abstract

Background The process of subchondral bone remodelling plays an imperative role in the progressive development of OA. Hyperoside (Hyp) is a flavonoid, which has a wide range of pharmacological effects. This study aims to explore the effect of Hyp on the subchondral bone to elucidate the therapeutic role of Hyp in medial meniscus destabilization (DMM) induced OA.Methods Firstly, we conducted histological research(HE staining, Safranin-O/Fast Green and Toluidine blue staining, TRAP staining, IHC) and microCT to test the ability of Hyp on cartilage degeneration and abnormal subchondral microstructural changes in the DMM-induced osteoarthritic mouse model. Secondly, In the in vitro experiments, RAW264.7 cells were induced to osteoblasts in the presence of different concentrations of Hyp and osteoclasts were labelled by TRAP staining. MC3TC-E1 cells were used to perform osteoinduction experiments in Osteogenic Induction Media (OIM). Osteogenic activity was observed through Alizarin red S staining, and mineralisation activity was observed through ALP staining. Last, Finally, the effect of Hyp on NF-κB pathways was studied using Western blot and immunofluorescence.Results Hyp decreased cartilage degeneration and improved BV/TV and Tb.Th structural parameters. It also reduced the number of TRAP-positive osteoclasts, nestin cells, and osterix cells in the subchondral bone. Additionally, Hyp Inhibits osteoclast formation and enhanced alkaline phosphatase activity and mineralization. Furthermore, the NF-κB signalling pathway related to osteoclasts was inhibited.Conclusion These results indicate that Hyp has potential therapeutic value for OA by modulating osteoclastogenesis and osteoblastogenesis in the subchondral bone.