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Over the last few years, immunotherapy targeting proinflammatory cytokines has been the main goal of research into rheumatoid arthritis (RA), and recently the new anti-(tumour necrosis factor) blocking agents have dramatically improved the course of the disease by stabilising the symptoms.1 However, this treatment has no effect on regeneration of articular cartilage damaged during the inflammatory process. The next challenge is thus to ensure cartilage repair through cell therapy and tissue engineering (fig 1). Tissue in the body is replaced by two main mechanisms. One is self repair by fully differentiated cells (healing), and the second is replacement with newly differentiated cells derived from stem cells. Recently, the regenerative potential of mesenchymal stem cells (MSCs) has been under intense investigation because of their ability for self renewal and differentiation to reconstitute muscle, cartilage, or bone.2
Articular cartilage is a complex tissue consisting of cartilage matrix and the chondrocytes that have produced the matrix during development. The matrix is composed of collagens and proteoglycan aggregates (aggrecan) which provide the architectural structure and biomechanical strength of the tissue. During RA pathogenesis, proinflammatory cytokines present in the rheumatoid synovial fluid activate metalloproteinase (MMP) secretion by chondrocytes and increase pericellular matrix degradation of these cells. Some of them (interleukin 1β and 6 (IL1β and IL6)) even display the synergistic ability to decrease aggregan chondral synthesis and hyaluronan/aggregan ratio in the extracellular matrix.3 4 However, proteoglycan depletion may be partially inhibited by IL1 receptor antagonist.5 Cartilage and bone degeneration in RA is also the result of the action of MMPs secreted into the synovial fluid by the synoviocytes. MMPs constitute a family of 18 endopeptidases, the secretion of which is stimulated by cytokines of the IL6 family (IL11, IL6, oncostatin M) through a protein called the …
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