In view of the important role of interstitial collagenase in the pathogenesis of rheumatoid arthritis (RA), we studied the expression of fibroblast-type collagenase in rheumatoid synovium and searched for its potential transcription factors, namely the oncoprotein c-fos and the early-growth-response gene-1 (egr-1), an inducible zinc-finger encoding gene.
We herein show the up-regulation of MMP-1 (interstitial collagenase) and MMP-3 (stromelysin) mRNAs of cultured synovial fibroblasts retrieved from rheumatoid arthritis (RA) patients in response to macrophage migration inhibitory factor (MIF).
To study the expression of collagenase 3 (matrix metalloproteinase 13 [MMP-13]) and collagenase 1 (MMP-1) in synovial fibroblasts from patients with rheumatoid arthritis (RA) when cultured within 3-dimensional collagen gels or coimplanted with normal cartilage in immunodeficient NOD/SCID mice.
Using a fibroblast-like synoviocyte cell line derived from a patient with rheumatoid arthritis, we examined the effects of gentle cyclic strain, focusing on the expression and activity of matrix metalloproteinase-1 (MMP-1) and MMP-13.
However, the spontaneous production of IL-6 and MMP-1 is suppressed only in the Ad-p21-infected RA synovial fibroblasts, indicating a novel role for p21 in RA.
Expression of DC-SIGN and its ligand, ICAM-3, is found in substantial amounts only in RA synovium, suggesting that their interaction is implicated in the additional activation of synovial macrophages that leads to the production of EMMPRIN and MMP-1.
However, incubation of RA synovial fibroblasts as well as OA synovial fibroblasts with staphylococcal PGs led to an up-regulation of CD54 (ICAM-1) surface expression and to increased expression of MMP-1, MMP-3, and MMP-13 mRNA.
To evaluate Fcgamma receptor (FcgammaR) expression on synovial macrophages from rheumatoid arthritis (RA) patients and to determine whether this expression correlates with the production of the proinflammatory cytokines tumor necrosis factor alpha (TNFalpha), interleukin-1beta (IL-1beta), IL-12, and matrix metalloproteinase 1 (MMP-1).
TNF-a stimulation induced IL-6 secretion by RA SFB (3-fold) and OA SFB (4-fold), as well as MMP-1 secretion (RA, 85-fold; OA, 29-fold), with significant differences between RA and OA.
Our data show that the functional promoter polymorphism in the MMP-1 promoter may not play an important role in the susceptibility of RA, but the polymorphism may be related to clinical phenotypes.
The matrix metalloproteinases MMP1 (interstitial collagenase) and MMP3 (stromelysin 1) are thought to be important in destructive joint changes seen in RA.
Silencing of NFkappaB1 by small interfering RNA abrogated the capacity of RA bone marrow CD34+ cells to differentiate into fibroblast-like cells and to produce MMP-1 and vascular endothelial growth factor upon stimulation with stem cell factor, granulocyte-macrophage colony stimulating factor and TNF-alpha without influencing their viability and capacity to produce beta2-microglobulin.
IL-1beta increased the transcriptional and translational levels of MMP-1 and MMP-13 in rheumatoid arthritis FLSs, whereas the levels of MMP-2 and MMP-9 were unaffected.