Acetylsalicylic Acid Combined With Diclofenac Inhibits Cartilage Degradation In Rabbit Models Of Osteoarthritis

Osteoarthritis is a kind of chronic joint disease characterized by articular cartilage degeneration and secondary bone hyperplasia. The diseased region is concentrated on knee, hip, and distal interphalangeal joints, which are burdened heavily. Nowadays, ageing has turned to more and more obviously. Thus OA has become a serious social problem which has influenced the public health.Pathogenesis of OA is related to aging, obesity, inflammation, trauma, joint overuse, metabolic disorders, and genetic factors. The guide to the diagnosis and treatment of osteoarthritis constituted by orthopedics branch of Chinese medical association cleared the aim of treatment for OA is to relieve pain, prevent and slow down disease progression, joint protection function, improve the quality of life. Overall principles of treatment are therapy combined drugs with non-drugs. Commonly used drugs include nonsteroidal anti-inflammatory drugs (NSAIDS), painkillers, viscoelasticity supplements, glucosamine, etc. Various drug therapies can only relieve symptoms, so the present study focuses on the various biological and biomechanical factors which can target against OA and can slow down the OA progression to the greatest extent. A large number of studies have shown that OA pathological mechanism is caused by various reasons of articular cartilage cell apoptosis and extracellular matrix degradation caused by the injury of system disease. Therapeutic targets are to slow or reverse chondrocytes apoptosis. Cartilage and synovial cell can highly express matrix metalloproteinases (MMPs).The dynamic balance between the organization for enzymes and matrix metalloproteinases inhibition (TIMPs) is broken. Under the influence of the mechanical load function and inflammatory factor etc, matrix composition dissociated from the cartilage and the lasting damage in protein, polysaccharide, eventually leads to the degradation of cartilage and destruction.In 1999, the FDA issued osteoarthritis study guide, including the application of animal models. The purpose of establishing OA model is to reproduce joint disease, and develop potential treatments. In this study, we choose the New Zealand white rabbit to duplicate human OA mode caused by trauma and establish the rabbit model of osteoarthritis. We give medication to the animals which are established models successfully. There are two kinds of drugs chosen to the experiment, acetyl salicylic acid and diclofenac sodium. Acetyl salicylic acid is a kind of antipyretic analgesics, which can be used for osteoarthritis and rheumatoid disease, also can inhibit platelet aggregation. Diclofenac, belongs to the non-steroidal anti-inflammatory drugs (NSAIDS). Since the 1960s, there are many reports about two drugs combination to treat osteoarthritis and rheumatoid arthritis, however, about the mechanism of combination as well as therapeutic targets, there are no detailed reports. This study hypothesizes that OA disease process is relevant to the changes of the factor like MMPs, TIMPs, IL-1β and NO, then explore the activity and expression of several cytokines during the process of the treatment of OA. This study will be divided into five parts.1. Experimental study to establish rabbits osteoarthritis model with Hulth method2. Effects of Acetylsalicylic acid combined with diclofenac on histology of rabbit model3. Effects of Acetylsalicylic acid combined with diclofenac on content of IL-1β and NO in arthritis synovial of rabbit model4. Effects of Acetylsalicylic acid combined with diclofenac on expression of MMP-3 and MMP-13 in arthritic cartilage cells of rabbit model5. Effects of Acetylsalicylic acid combined with diclofenac on expression of TIMP-1 in arthritic cartilage cells of rabbit modelObjective:To study the effects of different concentration of experimental acetylsalicylic acid combined with diclofenac on rabbit models of osteoarthritis of articular cartilage.Methods:Acetyl salicylic acid combined with diclofenac in accordance with different concentration into three groups 5mg/kg, 10mg/kg,20mg/kg, rabbit osteoarthritis model of 32 New Zealand white rabbits, score to each big white rabbit, were measured in synovial fluid NO, IL-1 beta content by kit, determination of MMP-3 WB method, the expression of the MMP-13 protein, expression determination of TIMP-1 by PCR mRNA, observed the changes of various indexes.Results:Different concentrations of the drug has good therapeutic effect on osteoarthritis of rabbit knee, can reduce the scores, reduce the content of NO, IL-1 beta, WB showed the downregulation of expression of MMP-3 and MMP-13, PCR found found the upregulation of TIMP-1 mRNA expression.Conclusion:The development of different concentrations ofacetyl salicylic acid combined with diclofenac can effectively inhibit rabbit osteoarthritis, and can inhibit NO, IL-1 beta, MMP-3, MMP-13, TIMP-1 expression, and thus play an important role in the treatment. In the process treatment of OA, we detected the activity and expression of several cytokines, then explored the molecular mechanism of the combination with the two drugs, thus laid a solid foundation for combination therapy. And the two drugs are of high quality and low price, greatly reduce the economic burden of patients. The focus of this study is here.