CD147 overexpression on synoviocytes in rheumatoid arthritis enhances matrix metalloproteinase production and invasiveness of synoviocytes

Rheumatoid arthritis (RA) is characterized by chronic proliferative synovitis, with hyperplasia of the synovial lining cells, inflammatory cell infiltration and angiogenesis in the sublining cell layer. Hyperplastic synovial lining cells overproduce such matrix metalloproteinases (MMPs) as MMP-1, MMP-2, MMP-3, MMP-9 and MT1-MMP, which may be involved in tissue remodeling during angiogenesis and cartilage destruction. Articular cartilage at the margins of the articular surface, to which synovium tissue can directly attach, is progressively degraded even in the disease's early stage. As macrophage-like synoviocytes (MLS) and fibroblast-like synoviocytes (FLS) are known as the most active cells and are close to the articular cartilage in a position to invade the cartilage, their expression of MMPs and their interaction have been reported to be related to cartilage destruction. Although IL-1 and tumor necrosis factor alpha are reported by some studies as key regulators of matrix degradation in RA, other molecules, such as CD147, are also thought to have played some regulatory role in RA pathogenesis [1-4]. But very few reports have been presented on CD147 functions in cartilage destruction.CD147, also called extracellular matrix metalloproteinase inducer and leukocyte activation-associated M6 antigen or HAb18G, was initially identified on the surface of human cancer cells and has been proven to stimulate the adjacent stromal cells to produce several MMPs [5,6]. CD147 is broadly expressed on hemopoietic and nonhemopoietic cell lines [7] and has the function of tissue remodeling. The expression of CD147 has been reported to be upregulated in the synovial membrane of RA patients [8,9]. In our previous study, we found that CD147 was expressed in synovium not only on the fibroblast-like cells, but also on peripheral monocyte-derived CD68+ macrophage-like cells [10].The study reported here was designed to investigate the expression of CD147 on FLS and THP-1 cells derived from