📇 Rhumatologue · Salarié

M Jean-Luc MERTENS

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16 articles scientifiques publiés — formation continue solide
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SalariéRPPS 10001129989

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Top publications · les plus citées

Medical and psychiatric conditions of alcohol and drug treatment patients in an HMO: comparison with matched controls

Archives of internal medicine · 2003

📚 181 citations🎯 RCR 6.27Top 5% NIH

Galectin-9 is an easy to measure biomarker for the interferon signature in systemic lupus erythematosus and antiphospholipid syndrome

Annals of the rheumatic diseases · 2018

📚 68 citations🎯 RCR 3.07Top 16% NIH

Inhibition of fibroblast activation protein and dipeptidylpeptidase 4 increases cartilage invasion by rheumatoid arthritis synovial fibroblasts

Arthritis and rheumatism · 2010

📚 62 citations🎯 RCR 1.69🔓 Open Access

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AbstractObjectiveSince fibroblasts in the synovium of patients with rheumatoid arthritis (RA) express the serine proteases fibroblast activation protein (FAP) and dipeptidylpeptidase 4 (DPP‐4)/CD26, we undertook the current study to determine the functional role of both enzymes in the invasion of RA synovial fibroblasts (RASFs) into articular cartilage.MethodsExpression of FAP and DPP‐4/CD26 by RASFs was analyzed using fluorescence‐activated cell sorting and immunocytochemistry. Serine protease activity was measured by cleavage of fluorogenic substrates and inhibited upon treatment with L‐glutamyl L‐boroproline. The induction and expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in RASFs were detected using real‐time polymerase chain reaction. Densitometric measurements of MMPs using immunoblotting confirmed our findings on the messenger RNA level. Stromal cell–derived factor 1 (SDF‐1 [CXCL12]), MMP‐1, and MMP‐3 protein levels were measured using enzyme‐linked immunosorbent assay. The impact of FAP and DPP‐4/CD26 inhibition on the invasiveness of RASFs was analyzed in the SCID mouse coimplantation model of RA using immunohistochemistry.ResultsInhibition of serine protease activity of FAP and DPP‐4/CD26 in vitro led to increased levels of SDF‐1 in concert with MMP‐1 and MMP‐3, which are downstream effectors of SDF‐1 signaling. Using the SCID mouse coimplantation model, inhibition of enzymatic activity in vivo significantly promoted invasion of xenotransplanted RASFs into cotransplanted human cartilage. Zones of cartilage resorption were infiltrated by FAP‐expressing RASFs and marked by a significantly higher accumulation of MMP‐1 and MMP‐3, when compared with controls.ConclusionOur results indicate a central role for the serine protease activity of FAP and DPP‐4/CD26 in protecting articular cartilage against invasion by synovial fibroblasts in RA.

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M Jean-Luc MERTENS

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Publications scientifiques (16) — classées par pathologie

Transversal7

Sclérodermie5

csDMARDs3

Lupus2

Risque cardio-vasculaire1

SAPL1

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