Scutelllarin Ameliorates Cartilage Degeneration In Osteoarthritis By Inhibiting The Wnt/?-catenin And MAPK Signaling Pathways

Background: Osteoarthritis(OA)is a low-grade inflammatory disease that changes from cartilage degeneration to pathological basis.Meanwhile,secondary changes in the bone and joint structure occur,characterized by narrow joint space,subchondral sclerosis,osteophyte formation around the joint,and ligament damage.Clinically,the knee joint is painful,pain in the upper and lower floors,joint ligament cysts,and joint effusion.Wait.Affecting the patients' daily life,it can be severely disabling,which not only brings a burden on personal and family life,but also increases socioeconomic costs.With the aging of the global population,the number of arthritis patients has increased year by year.According to a conservative estimate by the World Health Organization,there are currently about 250 million people with arthritis.However,there are no effective treatments for the treatment of OA in the clinic.It can only control pain and delay the operation time of knee replacement.With the in-depth study of basic medicine,it has been shown that the imbalance of catabolism of the extracellular matrix of cartilage causes OA cartilage regression One of the changing mechanisms,but the specific pathogenesis is still unknown.Therefore,exploring the pathogenesis of knee osteoarthritis and seeking effective treatment measures for its mechanism are the continuous efforts of global medicine.Objective Based on the research of catabolism imbalance,further explore the mechanism by which Scutellarin regulates chondrocyte synthesis and catabolism imbalance,according to the above research ideas,to provide new drug possibilities for the treatment of OA.Methods 1.Search the Pubmed database to provide a theoretical basis for Scutellarin treatment of OA;2.Collect cartilage tissue from patients undergoing knee replacement in the First Affiliated Hospital of Anhui Medical University,extract and culture chondrocytes,and identify cultured chondrocytes;3.IL-1? was added to the chondrocyte culture supernatant to simulate an in vitro OA model,and then the chondrocytes were treated with SCU at different concentrations,and the cell viability was detected to select a suitable concentration;4.Detect anabolic markers(Collagen II,Aggrecan)and catabolic markers(MMP-1,MMP-13,ADAMTS-5)and Wnt / ?-catenin in simulated OA chondrocytes by q RT-PCR and Western blot.And expression differences of MAPK signal pathway related molecules.5.DMM(medial meniscus resection)was used to make the model in C57 BL / 6 mice;Microinjection of SCU in the joint cavity of mice was performed.The mice were sacrificed 8 weeks and 12 weeks later to remove the knee joints for pathological section.Safranine O-fast green staining and immunohistochemical detection of expression differences.Results 1.The expressions of MMP-1,MMP-13,and ADAMTS-5 in the SCU-treated cell group and the blank control group were significantly reduced compared to the IL-1?-treated group by q RT-PCR and Western blot;2.Western blot was used to detect Wnt / ?-catenin and MAPK signaling pathway activating protein in the SCU-treated cell group,blank control group and IL-1? alone treatment group.The SCU-treated cell group and blank control group had ?-catenin and p-P38 are significantly reduced;3.Immunofluorescence was used to detect the ?-catenin nucleation in the SCU-treated cell group,the blank control group and the IL-1? alone treatment group.reduce;4.The knee joint pathological sections of the SCU-treated mice group,the blank control group and the DMM-treated mouse group were detected by Saffron O-fast green staining.Become significantly reduced;5.Wnt / ?-catenin and MAPK signaling pathway activating protein were detected by immunohistochemical staining in the SCU-treated mice group,the blank control group and the DMM-treated mouse group.The expression of ?-catenin and p-P38 in the mouse group was significantly reduced.Conclusion Scutellarin can inhibit the expression of MMP-1,MMP-13,ADAMTS-5 in human osteoarthritis chondrocytes,and promote the synthesis of Aggrecan and Collagen II,and relieve knee cartilage degeneration.This effect may be related to its inhibition of Wnt / ?-catenin and MAPK signal pathway.