The Role And Mechanism Of MMPs In Osteoarthritis Caused By Articular Cartilage Destruction

The incidence of osteoarthritis OA involves many factors,which vary in the process of its gradual formation.It is a disease mainly manifested in the joints,among which mechanical damage and joint degeneration are the important factors leading to osteoarthritis.The characteristics of osteoarthritis include not only the changes of cartilage tissue in the joint,but also the changes of inflammation and surrounding tissue.Under the effect of long-term and repeated internal and external pathogenic factors,the degree of joint surface structure damage is gradually aggravated,and joint deformity eventually leads to the loss of joint function,which makes the patients' quality of life and sports ability greatly reduced.The gradual loss of joint function is closely related to the abnormality of articular cartilage when many pathogenic factors cannot be completely avoided.The surface of the joint is covered with a layer of cartilage that protects the subchondral bone and supports the mechanical framework of the joint.Damaged cartilage is further damaged in several ways.In this process,the changes in the extracellular matrix of chondrocytes are not optimistic.Matrix metalloproteinases degrade various substances such as collagen,elastin and polyproteoglycan in the matrix,especially collagen and elastin,which maintain the structure of cartilage skeleton.MMPs is composed of propylene peptide zinc dependent enzyme family,is divided into several subtypes,and the formation of multiple combined with matrix protein in the structure of the domain,each MMPs contains a number of different functional areas of domain structure,which has the structure of the catalytic activity area is a Zn2+ depend on the special structure of the domain,the auxiliary function of hinge and heme binding protein structure.During normal body operation,chondrocytes secrete a very small amount of MMPs and maintain a relative balance with TIMP,to ensure that cartilage tissue is in a healthy state for damage and repair.The experimental results showed that when the equilibrium state of cartilage was broken and gradually changed to form osteoarthritis,the gene expression of MMPs was up-regulated and its secretion was abnormally increased,which accelerated the degradation of extracellular matrix and resulted in the continuous loss and destruction of collagen and elastin.In the pathological state,if it cannot be adjusted in time to adapt to the changes of the body or it is very likely to lead to the aggravation of cartilage damage,the damage of cartilage tissue will eventually be irreversible,and the result will be the gradual formation of OA.It is very important to explore the metabolic biological characteristics of cartilage and to find ways to inhibit the damage and repair of cartilage.OA is a disease mainly characterized by middle-aged and elderly people,and its repair ability is extremely limited.Once the cartilage tissue is damaged,it may not be able to recover.In particular,when multiple influencing factors cannot be terminated,after tissue injury,there will be more and more injuries,repeated,pathological and malformed cartilage repair,which will eventually lead to joint deformity in the long run.In severe cases,it will even affect patients' quality of life and sports ability.In China,the population structure has changed a lot,and the population density has increased rapidly.With the increase of age,the overall repair level of the body declines,and the risk of injury increases,the repair process after the injury of articular cartilage becomes extremely difficult.We must deal with the root of the problem,prevent the disease before it occurs,increase the popularization of community medical knowledge.Don't shy away from medical treatment,early detection,research and discovery of new treatment methods to reduce the difficulty of treatment.The characteristics of osteoarthritis and age,weight,occupation are closely related.In the investigation and statistics of osteoarthritis patients,it was found that in the treatment of osteoarthritis patients,arthroscopic surgery in the patients with articular cartilage lesions accounted for more than 60%,among which full layer of cartilage injury accounted for 11%.In the process from the onset of symptoms of articular cartilage injury to the formation of osteoarthritis,the pathological changes of the disease,the occurrence and development of destruction of articular cartilage will be regulated by a variety of inflammatory factors and signal channels,forming a cascade of amplifying circulatory network.The results showed that pathogenesis of cartilage injury are closely related to matrix metalloproteinases.Therefore,in order to clarify the influence of abnormal MMPs on articular cartilage,we hope to study the animal model of osteoarthritis,identify the relationship between MMPs and articular cartilage tissue damage,and find out the mechanism of cartilage tissue damage regulation and the changes of MMPs in the tissue during this process.To verify the damage of MMPs to cartilage tissue.In addition,we hope to analyze the mechanism of action and molecular pathway of MMPs by regulating the gene expression of MMPs or interfering with it through TIMPs inhibitors.An in-depth understanding of MMPs will open a new way for the diagnosis and treatment of OA.Therefore,the purpose of this study is to explore the role of MMPs on articular cartilage injury in osteoarthritis and its mechanism,and to seek a new method for the diagnosis,treatment and prognosis of OA.The main content of this project is to make the association between abnormal expression of MMPs and osteoarthritis caused by articular cartilage injury was determined,through animal experiments.Objective:The effect of MMPs on articular cartilage injury and its correlation with osteoarthritis were studied by Hartley guinea pigs.Experimental methods:Selection of subjects is SPF Hartley guinea pigs,purchase from Beijing tong lihua experimental animal technical co.LTD,is provided by the Yangtze university medical center for experimental animals and raise the generation of 30 male guinea pigs,weight 300� 100 g.The guinea pigs were randomly divided into the control group A and injected with the same amount of normal saline in the articular cavity,and the experimental group B(B1 and B2)and injected with MMPs and TIMP biologic agents respectively.Feeding under the same healthy feeding conditions.After feeding for 2,4,6,8 and 10 weeks,guinea pigs were put to death and their data were collected,with 2 guinea pigs in each group.We need to collect the articular cartilage of guinea pigs at different stages of the experiment and make pathological sections.Changes in cartilage tissue were observed under a light microscope.Detect the changes of collagen type ? in cartilage tissue and the expression level of IL-1??TNF-?.Results:The results of animal experiments showed that the cartilage degeneration of guinea pig knee joints was more serious in the experimental group injected with MMPs than in the control group injected with normal saline.The cartilage loses its normal elasticity,and there are tiny cracks,even exfoliated patches,and osteophytes around the joints.Microscopically,chondrocytes were reduced,tears and microfibrosis were observed near the fissure,etc.With the time of experiment,extend the content of collagen type ? declines gradually,the differences between the two(P<0.05),with statistical significance.The results of the changes in serum levels of IL and TNF showed that there were differences between the experimental group and the control group(P<0.05);Compared with the control group,the progress of cartilage damage was slowed in the experimental group injected with TIMP.The loss of collagen type ?becomes slow,and knee joint degeneration has been alleviated to some extent.Compared with the control group,there was a difference between the two groups(P<0.05),which was statistically significant.There was no significant difference between the experimental group and the control group in terms of serum IL-1??TNF-?(P>0.05).There is no statistical significance.Conclusion:MMPs main effect is to change of extracellular matrix,to break down ?type collagen,to destroy the biological structure of cartilage.MMPs accelerate the destruction of cartilage tissue,result the loss of joint function and ultimately lead to osteoarthritis.The use of TIMP inhibitors can alleviate the lesions of osteoarthritis to a certain extent.