The Effect Of Lactoferrin On The Production Of MMPs,COX-2 And PGE2 In Human Osteoarthritis Synovial Fibroblasts Induced By IL-1?

Objective: Osteoarthritis(OA)is a degenerative disease of joint tissue,the main characteristic of which is the imbalance of anabolic metabolism of joint tissue and the degradation of extracellular matrix tissue.In OA pathophysiological process,synovial(SM)lesions play an important role,SM is also an important source of inflammatory and joint matrix degradation of the decomposition of metabolites,SM tissue lesions can not only lead to a significant reduction in the concentration of protective factors in the joint tissue,It can also cause an increase in the factors that have matrix degradation in the joints.In the pathophysiological process of OA synovitis,it is accompanied by the production of many inflammatory cytokines.In these inflammatory factors,interleukin-1?(IL-1?)is the most known inflammatory factor for the study of OA lesions,which plays a key role in the pathophysiology of OA synovial fibroblasts(OA FLS).It can be contributed to the production of inflammatory cytokines interleukin-1?(IL-1?)MMPs,COX-2,PGE2,these inflammatory media have the role of catabolism on OA.Lactoferrin(LF)has antibacterial,anticancer,antioxidant,antiviral,anti-inflammatory and other effects,mainly in milk,tears and saliva,bronchial and intestinal secretions,as well as neutrophils granules,especially in the body where inflammation occurs,LF expression significantly increased.Therefore,the purpose of this experiment is to study the effects of LF on MMPs,COX-2 and PGE2 induced by IL-1? in osteoarthritis synovial fibroblasts,and to provide reference for OA therapy.Methods: The human OA synovial fibroblasts were isolated and cultured,and the cells of three generations and above were taken for experiments,and the experiments were divided into blank control group,induction group and induction and treatment group.The blank control group was not treated with any drugs,and the induction group joined IL-1?(NG/ML)to induce the addition of IL-1?(100,200,400?G/ML)to the treatment group.According to the characteristics of fibroblasts specificexpression VM,the characteristics of cultured cells were identified by cellular immunofluorescence method staining,and the effect of different concentrations of lactoferrin on the activity of OA synovial fibroblasts was detected by CCK8 method,and real-time quantitative PCR(RT-PCR)and Western Blot(WB)method was used to detect the effect of lactoferrin on the expression of MMPs,COX-2 and PGE2 in IL-1? induced human OA synovial fibroblasts,and the effect of PGE2 expression was measured by ELISA method.Results: The results of cellular immunofluorescence staining showed that the cultured cells were fibroblasts,and the results showed that LF had no significant toxic effect on synovial fibroblasts in a certain concentration range,and there was no significant difference in the CCK8;RT-PCR and WB results suggest that LF inhibits MMPs and COX-2 protein and gene levels in IL-1? induced human OA synovial fibroblasts,ELISA results suggest that LF has inhibitory effect on the PGE2 of IL-1?induced human OA synovial fibroblasts and has obvious concentration dependence.Conclusion: When the OA synovial tissue lesions,inflammatory factor IL-1?can stimulate FLS to produce MMPs,cyclooxygenase-2 and PGE2 and other inflammatory media,they interact to induce changes in articular cartilage tissue,thus speeding up the process of OA lesions.The results of this experiment show that LF can reduce IL-1? induced synovial cells to produce MMPs,cyclooxygenase 2 and PGE2,and provide molecular basis for future intervention of SM lesion process to control or slow down the progress of OA.