Expression and function of junctional adhesion molecule-C in human and experimental arthritis

Junctional adhesion molecule-C (JAM-C) is an adhesion molecule involved in transendothelial migration of leukocytes. In this study, we examined JAM-C expression in the synovium and investigated the role of this molecule in two experimental mouse models of arthritis. JAM-C expression was investigated by reverse transcriptase-polymerase chain reaction and immunohistochemistry. The effects of a monoclonal anti-JAM-C antibody were assessed in antigen-induced arthritis (AIA) and K/BxN serum transfer-induced arthritis. JAM-C was expressed by synovial fibroblasts in the lining layer and associated with vessels in the sublining layer in human and mouse arthritic synovial tissue. In human tissue, JAM-C expression was increased in rheumatoid arthritis (RA) as compared to osteoarthritis synovial samples (12.7 ± 1.3 arbitrary units in RA versus 3.3 ± 1.1 in OA; p < 0.05). Treatment of mice with a monoclonal anti-JAM-C antibody decreased the severity of AIA. Neutrophil infiltration into inflamed joints was selectively reduced as compared to T-lymphocyte and macrophage infiltration (0.8 ± 0.3 arbitrary units in anti-JAM-C-treated versus 2.3 ± 0.6 in isotype-matched control antibody-treated mice; p < 0.05). Circulating levels of the acute-phase protein serum amyloid A as well as antigen-specific and concanavalin A-induced spleen T-cell responses were significantly decreased in anti-JAM-C antibody-treated mice. In the serum transfer-induced arthritis model, treatment with the anti-JAM-C antibody delayed the onset of arthritis. JAM-C is highly expressed by synovial fibroblasts in RA. Treatment of mice with an anti-JAM-C antibody significantly reduced the severity of AIA and delayed the onset of serum transfer-induced arthritis, suggesting a role for JAM-C in the pathogenesis of arthritis

Serum MMP-3 in rheumatoid arthritis: correlation with systemic inflammation but not with erosive status

OBJECTIVE: Metalloproteinases (MMP) play an important role in the remodelling of the extracellular matrix. However, evidence that they are responsible for tissue damage in pathological situations remains circumstantial. Stromelysin (MMP-3) production is increased in rheumatoid arthritis (RA), and has been proposed as a marker of joint damage. The relevance of serum levels of MMP-3 to erosions in RA was studied. METHODS: Fifty-three patients with active RA of > 5 yr duration and with available X-rays were stratified according to disease duration. Hand X-rays were scored for erosions. Patients were then classified into upper and lower quartiles. Serum MMP-3 levels were compared between these two groups. RESULTS: No significant differences in serum MMP-3 were seen between high and low eroders. A statistically significant correlation was observed between sMMP-3 and erthyrocyte sedimentation rate and C-reactive protein. CONCLUSIONS: Serum MMP-3 is not an independent marker of joint damage, but is correlated with systemic inflammation. Its precise role in joint damage in RA remains to be elucidate

Exacerbation of antigen-induced arthritis in urokinase-deficient mice.

In rheumatoid arthritis, synovial expression of urokinase (uPA) activity is greatly increased (Busso, N., V. Péclat, A. So, and A. -P. Sappino. 1997. Ann. Rheum. Dis. 56:550- 557). We report the same effect in murine antigen-induced arthritis. uPA-mediated plasminogen activation in arthritic joints may have deleterious effects via degradation of cartilage and bone matrix proteins as well as beneficial effects via fibrin degradation. We evaluated these contrasting effects in vivo by analyzing the phenotype of uPA-deficient (uPA-/-) and control mice during antigen-induced arthritis. Joint inflammation was comparable in both groups up to day 3 and subsequently declined in control mice, remaining significantly elevated in uPA-/- mice on days 10 and 30 after arthritis onset. Likewise, synovial thickness was markedly increased in uPA-deficient mice persisting for up to 2 mo, whereas it subsided in control animals. Bone erosion was exacerbated in uPA-/- mice on day 30. By contrast, no difference in articular cartilage proteoglycan content was found between both groups. Significantly increased accumulation of fibrin was observed by day 30 in arthritic joints of uPA-/- mice. We hypothesized that synovial fibrin deposition plays a role in joint inflammation. Accordingly, defibrinogenation of uPA-/- mice by ancrod significantly decreased the sustained joint inflammation. All the above observations were reproducible in plasminogen-deficient (Pln-/-) mice. In conclusion, synovial fibrin deposition plays a role as a nonimmunological mechanism which sustains chronic arthritis

Expression of junctional adhesion molecule-C (JAM-C) in human arthritic synovium

<p><b>Copyright information:</b></p><p>Taken from "Expression and function of junctional adhesion molecule-C in human and experimental arthritis"</p><p>http://arthritis-research.com/content/9/4/R65</p><p>Arthritis Research & Therapy 2007;9(4):R65-R65.</p><p>Published online 5 Jul 2007</p><p>PMCID:PMC2206366.</p><p></p> Expression of JAM-C was examined by immunohistochemistry in human osteoarthritis (OA) and rheumatoid arthritis (RA) synovial tissue. The panels labeled 1 show the original magnification (× 100). The panels labeled 2 show expression of JAM-C in the synovial lining layer (magnification × 400), and panels labeled 3 show JAM-C associated with blood vessels in the sublining (magnification × 400). The panels labeled 4 show negative control sections incubated with preimmune serum. Scale bars = 60 μm (panels 1 and 4) and 15 μm (panels 2 and 3). Quantification of JAM-C expression in OA and RA synovial tissues. JAM-C immunohistochemical synovial tissue sections from four different OA and RA patients were scanned, and the surface of immunoreactive areas was determined and expressed as the percentage of the surface of the image examined. Results are expressed as the mean ± standard error of the mean. *< 0.001 OA versus RA as assessed using the Wilcoxon rank sum test. Reverse transcriptase-polymerase chain reaction (PCR) analysis of mRNA expression in human synovial tissue samples and in cultured human synovial fibroblasts. A representative agarose gel electrophoresis of PCR products is shown. bp, base pairs; HO, polymerase chain reaction negative control; hSF1 and hSF2, human rheumatoid arthritis synovial fibroblast cultures from two different patients used after the third passage; OA, osteoarthritis synovial tissue; RA, rheumatoid arthritis synovial tissue; RT neg, non-reverse-transcribed sample