Function Analysis Of Rheumatoid Arthritis Pathogenesis-Associated Protein DDR2

Rheumatoid arthritis (RA) is a chronical autoimmune disease whose etiology and mechanism are not well defined. The progress of RA is characteristic with secretion in acute phase and synovial proliferations in chronical phase, suggesting its sophisticated mechanism with participation of many cells, cytokines, and enzymes.DDR2 is a newly identified receptor protein tyrosine kinase, which is composed of three parts: DR region on the N terminus, a long justatransmembrane region (JM) between DR region and transmembrane region, and intracellular region in cytoplasma. The discoidin domain in extracellular region can recognize and bind to collagens, and play important roles in cellular proliferation and differentiation, invasiveness and metastasis. In previous studies of DDR2 function in RA during the past few years, we found that: (1) DDR2 expression in RA synovium is higher then OA synovium; (2) Besides expression in synovium in synovial tissues, DDR2 is expressed highly in immunocytes as well; (3) High MMP-1 expression is sustained in RA synovium cultured in vitro, whereas supernatant of OA cultured cells is not; (4) DDR2 ligand is fibroid collagens (type I, II, and III), and the interaction of collagens and DDR2 can intermediate cellular proliferation and up-regulates matrix metallloproteinase 1 (MMP-1) and MMP-2 expression in cellular...