The Preliminary Research Of Matrix Metalloproteinase-2/-9 Participate In Human Synovial Pannus Of Rheumatoid Arthritis

Research background and objective:Rheumatoid arthritis(RA) is a chronic generalized autoimmune disease, characterized by invasive joint inflammation. The pannus formation as the most characteristic pathological change of RA could also be viewed as non-malignant hyper-proliferative disease, pushing the progression of RA by cartilage and bone erosion, and leading to irreversible destruction of joint structure and function.Matrix metalloproteinases(MMPs),one of mostimportant enzyme series on regulate the dynamic equilibrium of extracellular matric(ECM),participate in embryonic growth and tissue remodeling as well as many pathological processes such as RA,tumor progression,atherosclerosis and so on.The expression levels of MMPs significantly associated RA disease progression,in which the gelatinases, mmp-2 and MMP-9, role important roles on the one hand,they degrade the main components of articular cartilage,such as gelatine,collagens,elastin and vitronectin,on the other hand,they could also process several bio-active factors, apoptotic chemokines, and cell signaling factors, which strengthen the immune responses. Moreover,MMP-2 and MMP-9 have been shown critical contributions in intra-tumor angiogenesis and invasion of tumor progression. As we know, the pannus with excessive angiogenesis behave in tumor-like fashion, therefore we herein suspected that they might also play important roles in the angiogenesis as well as the pannus formation of RA.In the present study, we aim to characterize the structure of RA pannus at active stage and the immunolocalization of MMP-2 and MMP-9 in RA pannus, in order to investigate their roles of in angiogenesis process and pannus formation of RA.Material and Methods:(1) The synovium tissues of the knee joint from three patient with RA at active stage were collected by arthroscopic biopsy in the Department of Orthopedics of The third affiliated hospital of Soochow University,(2) 3 tissue samples mentioned above whichwere fixed by formalin, embedded by paraffin are performed using were cut into consecutive 3-μm-thick sections for the immunohistochemical and immunofluorescence staining,(3) we use the con-focal scanning methods to characterize the immunolocalization of MMP-2 and MMP-9 in RA synovium tissues.Result:Under optical microscope, we found high expression of MMP-2 and MMP-9 as well as the pannus which was composed of rich micro vessels, synoviocytes and immune cells in RA synovium tissues at active stage. Moreover, our results by con-focal scanning also showed that MMP-2 and MMP-9 immunostaining could be found in synoviocytes and vascular endothelial cells. Moreover, our con-focal scanning also showed that MMP-2could be found in infiltrating CD14+ monocytes and CD68+ macrophages, and MMP-9could be found in infiltrating CD68+macrophages in RA synovium tissues, while weak or negative staining of these two MMPs could be found in infiltrating CD19+B cells and CD3+T cells in RA synovium.Conclusion:our finding suggests that both MMP-2 and MMP-9 expressed by synoviocytes and vascular endothelial cells, as well as certain infiltrating immune cells role importantly in the angiogenesis and pannus formation in RA progression.