Expression And Significance Of TNF-α、PGE2and MMP-9in The Knee Synovium Of Osteoarthritis

Background and purposeOsteoarthritis (OA) is a chronic,progressing degenerative disease of articular cartilage. It is a common clinical disease, often caused joint pain, swelling and dysfunction, the most severely results are articular deformities and disability which significantly affect the patient’s quality of life. At present, in the world especially in China the aging of the population is more and more apparent; osteoarthritis has become an important disease which affects the quality of life in older persons. According to statistics, OA has become the second main disease after cardiovascular and cerebrovascular diseases affecting the quality of life of the elderly. But the pathogenesis has not yet been fully understood, it is generally thought that there are a variety of factors of OA, including genetic factors, trauma, age, obesity, endocrine, cell factor, matrix metalloproteinases, and so on, and these factors interact with and influence each other. At present the research of OA pathogenesis mainly lies in cytokine, genes, cartilage histology and some metalloproteinases. In this experiment we chose TNF-α, PGE2cytokines and matrix metalloproteinase-9(MMP-9) as our reseaching factors. Immunohistochemical techniques was used to study their expression and correlation in the different stages of OA which could further elucidate the pathogenesis of OA and provide a theoretical basis for early diagnosis and early treatment.Materials and methods:All the synoviums are from the patients in orthopaedic of the first affiliated hospital of Zhengzhou University from July to November2011who had the knee surgery. OA patients were diagnosed using the proposed criteria from American College of Rheumatology, and we used Kellgren X-ray diagnostic criteria to pick out18cases in early stage,22cases in advanced stage who underwent arthroscopic operation or joint replacement, then we took the intraoperative synoviums. At the same time we selected15synoviums from8fresh meniscus injured patients and7fork ligament injured patients as control group. We washed the synoviums2-3times with physiological saline water after operation, cutted them into0.5cm3pieces, then we fixed them in10%paraformaldehyde, embedded in paraffin, and sliced them continuously into4-5μ m thickness sections which were seted aside. One slice which was examined by means of routine HE staining and light microscope was selected randomly respectively from each of the three groups. The remaining slices were examined by means of SP immunohistochemical staining for TNF-a, PGE2and MMP-9and light microscope. Useing Leica testing and analysis system to detect and analyze the immunohistochemical results integral optical density (IOD). Measurement datas were expressed by x±s, and SPSS17.0statistical software was used to analyze and process the datas. Single factor analysis of variance LSD-t was used to test differences of average values in the three groups for each test index, and MMP-9protein IOD was compared to PGE2, TNF-a protein IOD value respectively with Pearson product-moment correlation analysis. With α=0.05for inspection standards, P<0.05for the difference with a statistical significance.Results1. TNF-α, PGE2and MMP-9were only expressed little in the synovial tissues of the control group and weakly positive expressed in the mild-moderate lesion groups in which the cytoplasm was stained light brown yellow; in the severe lesion group they were strongly positive expressed and the cytoplasm was in deep tan.2. In the mild-moderate OA groups, IOD of TNF-a, PGE2and MMP-9protein was significantly higher than the normal control group (P<0.05), severe lesion group was higher than mild-moderate disease groups (P<0.05) and control group (P<0.05).3. In all of the OA groups, pearson correlation coefficient r=0.883between MMP-9and TNF-a, pearson correlation coefficient r=0.847between MMP-9and PGE2(P<0.01), the differences were statistically significant, the expression of TNF-a and PGE2were positively correlated with MMP-9in OA synovium.Conclusion1. TNF-a, PGE2and MMP-9in the OA synovium were expressed higer than than the normal group. The situation of expression has a positive correlation with the course and symptom severity of disease.2. TNF-a and PGE2can both increase the expression of MMP-9, resulting in the MMPs/TIMPs imbalance, and then caused degeneration of the articular cartilage, and ultimately lead to OA occurrence and progressive exacerbation.