Immunolocalization Of Membrane-type 1 MMP In Human Rheumatoid Synovium Pannus

Research background and objective:Rheumatoid arthritis(RA) is a chronic autoimmune inflammatory disease of unknown aetiology, reveals progressive destruction of bone and articular cartilage with functional impairment and disability, which was characterized by synovial inflammation, hyperplasia and pannus formation. Pannus as a characteristic change of RA, mainly composed of neovascularization, synovial hyperplasia, inflammatory cells, the angiogenesis is the key to form and maintain pannus. Neovascularization can provide nutrients and oxygen to the hyperplasia of the synovial tissue and maintain chronic inflammation. Angiogenesis is closely associated with the destruction of the bone and cartilage, studies have proved that inhibit the synovial neovascularization can reduce arthritis disease activity score.MMPs are a group of zinc-dependent endopeptidases, which can direct degradation of bone and cartilage and through stimulation of endothelial cells, make the pannus formation, increase of cartilage pannus invasion, participate in articular cartilage and bone tissue degradation and destruction. At present a large number of studies have found that MT1-MMP play an important role in the development of tumor, and RA invasive growth within the articular cartilage in the form of "tumor". MT1-MMP has been shown highly expressed at the pannus-cartilage junction of RA joints.In the present study, we focused on the study of the immunolocalization of MT1-MMP in the angiogenesis and the pannus formation in RA synovium tissues.Material and Methods:The synovium tissues of the knee joint from patients with RA at active stage were collected by arthroscopic biopsy in the Department of Orthopedics of The third affiliated hospital of Soochow University, tissue samples mentioned above which were fixed in 10% formalin, dehydrated,embedded in paraffin wax for sectioning at 3μm using a microtome for the immunofluorescence staining and use the con-focal scanning technique to characterize the immunolocalization of MT1-MMP in RA synovium tissues.Result:RA synovial tissue with HE staining show obvious synovial cell proliferation, angiogenesis and a large number of inflammatory cells infiltration, the characteristic pathological change of RA —pannus. Our results showed that the positive MT1-MMP immunostaining could be found in synoviocytes, vascular endothelial cells, infiltrating macrophages and monocytes in RA synovium tissues, while weak or negative expression could be found in infiltrating T cells, B cells and NK cells, respectively. Moreover, the Ki-67+ highly proliferating synoviocytes also showed higher MT1-MMP expression in RA synoviocytes.Conclusions:The aberrant expression of MT1-MMP in synoviocytes as well as infiltrating immune cells in RA synovial tissues may contribute to the proliferation of the synoviocytes, and the angiogenesis and the pannus formation in RA pathological progression. We thus believe that MT1-MMP can be a target molecule for potential therapeutic intervention for RA.