Study On The Effect Of Inhibition Of Notch Signaling Pathway On The Progression Of Knee Osteoarthritis In Rats

Backgrounds and Objective:Osteoarthritis of the knee(KOA)is the highest incidence of joint disease in the elderly.With the aging of the population in our country,the number of patients with osteoarthritis of the knee is increasing.The main symptoms of KOA are joint pain,limited joint activity,deformity,etc.It brings great pain and a heavy financial burden to the patient,seriously affects the quality of life of the elderly.At present,there is no good method for the treatment of osteoarthritis of the knee,the main treatment means to stay in early control symptoms,and the later surgery is performed.So scholars and doctors have paid more and more attention to the research on the development of osteoarthritis in the knee joint.Current research suggests that the development of osteoarthritis of the knee is related to multiple signaling pathways.Among them,Notch signaling pathway was confirmed to participate in the differentiation and metabolism of chondrocytes.,it plays an important role in the development of chondrocytes.,so the study of Notch signaling pathway plays an important role in the prevention and treatment of knee osteoarthritis.The purpose of this experiment is to investigate the effects of Notch signaling pathway during the progress of knee osteoarthritis in rats.Methods:In this study,we chose rats to do the body experiment because of its anatomical structure of knee joint height similarity to human.We established the knee osteoarthritis model of rat by the surgery way that cut off the anterior cruciate ligament,medial collateral ligament and also remove the medial meniscus of the rat right leg.Randomly divided the rats did not undergo surgery into 6 weeks blank group,8 weeks blank group;and randomly divided the rats operated into 6weeks operation group,6 weeks suppression group,8 weeks operation group,8 weeks suppression group.Pretreated rats of corresponding groups with injecting Notch signaling pathway inhibitor DAPT into knee joint cavity.6 weeks and 8 weeks after surgery,the corresponding group rats were executed,and the femoral medial condyle of the knee joint of the right hind leg was taken as a specimen.HE staining and immunohistochemistry were used to analyze the expression of matrix metal protein-13(MMP-13)and type ?collagen(Col ?)within knee joint cartilage of each group.Then,we compared the severity of knee osteoarthritis between different groups and studied the effects of inhibiting Notch signaling pathway on the development of knee osteoarthritis in rats.Results: The expression of MMP-13 in the knee joint cartilage of 6 weeks operation group was decreased,when compared with 8 weeks operation group.,while the expression of Col ? was increased,the difference between groups was statistically significant(p<0.05);The expression of MMP-13 in the knee joint cartilage of 6 weeks inhibition group was decreased when compared with 6 weeks operation group;while the expression of Col ? was increased the difference between groups was statistically significant(p<0.05),and this trend was also shown in 8 weeks inhibition group vs.8 weeks operation group the difference between groups was statistically significant(p<0.05).Conclusion: Inhibiting Notch signaling pathway decreases MMP-13 expression and Col ? damage,reduces knee osteoarthritis of rats.