Functional analysis of discoidin domain receptor 2 in synovial fibroblasts in rheumatoid arthritis

In order to know whether any protein tyrosine kinase (PTK) is involved in the over-proliferation and erosiveness of synovial fibroblasts (SF) of rheumatoid arthritis (RA) patients, RT-PCR and RNA dot blotting were done to analyse PTKs profile in RA SR Platelet-derived growth factor receptor A (PDGFRA), insulin-like growth factor 1 receptor (IGF-1R), Janus kinase I (JAK1), TYK2, discoidin domain receptor 2 (DDR2), and Lyn were expressed in SF, and the expression of PDGFRA, IGF-1R, and DDR2 in SF of RA were higher than that of osteoarthritis (OA, as control). Immunobloting and gelatinase zymography showed that DDR2 in RA SF, which still secreted active matrix metalloproteinase 1 (MMP-1) in vitro, were in active form. Stimulation of collagen 11 could make NIH-3T3 cells (as control) produce MMP-1, which could be inhibited by soluble extracellular part of DDR2. These results indicated that the overexpression of MMP-1 in RA SF might be related to the activation of DDR2, and collagen 11, act as DDR2 ligand, might be one of the stimulators of the over-expression of MMP-1 of RA SF. (C) 2002 Elsevier Science Ltd. All rights reserved.