Matrilin-3 activates the expression of osteoarthritis-associated genes in primary human chondrocytes

Klatt, Andreas R.; Klinger, Gabriele; Paul-Klausch, Brigitte; Kühn, Gertrud; Renno, Joerg H.; Wagener, Raimund; Paulsson, Mats; Schmidt, Joachim; Malchau, Gebhart; Wielckens, Klaus

doi:10.1016/j.febslet.2009.10.035

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Volume 583, Issue 22 , Pages 3611-3617, 19 November 2009

Matrilin-3 activates the expression of osteoarthritis-associated genes in primary human chondrocytes

Edited by Laszlo Nagy

Andreas R. Klatt
- Institute for Clinical Chemistry, University of Cologne, Germany
- Corresponding author. Address: Institut für Klinische Chemie, Universität zu Köln, Kerpener Str. 62, 50924Köln, Germany. Fax: +49 221 478 5273.
Gabriele Klinger
- Institute for Clinical Chemistry, University of Cologne, Germany
Brigitte Paul-Klausch
- Institute for Clinical Chemistry, University of Cologne, Germany
Gertrud Kühn
- Institute for Clinical Chemistry, University of Cologne, Germany
Joerg H. Renno
- Institute for Clinical Chemistry, University of Cologne, Germany
Raimund Wagener
- Center for Biochemistry, Medical Faculty, University of Cologne, Germany
Mats Paulsson
- Center for Biochemistry, Medical Faculty, University of Cologne, Germany
- Center for Molecular Medicine Cologne (CMMC), University of Cologne, Germany
- Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Germany
Joachim Schmidt
- Dreifaltigkeitskrankenhaus, Cologne, Germany
Gebhart Malchau
- Institute for Clinical Chemistry, University of Cologne, Germany
Klaus Wielckens
- Institute for Clinical Chemistry, University of Cologne, Germany

Received 4 September 2009; received in revised form 12 October 2009; accepted 12 October 2009. published online 19 October 2009.

Abstract

Here, we tested the matrilin-3-dependent induction of osteoarthritis-associated genes in primary human chondrocytes. Matrilin stimulation leads to the induction of MMP1, MMP3, MMP13, COX-2, iNOS, IL-1β, TNFα, IL-6 and IL-8. Furthermore, we show the participation of ADAMTS4 and ADAMTS5 in the in vitro degradation of matrilin-3. We provide evidence for a matrilin-3-dependent feed-forward mechanism of matrix degradation, whereby proteolytically-released matrilin-3 induces pro-inflammatory cytokines as well as ADAMTS4 and -5 indirectly via IL-1β. ADAMTS4 and ADAMTS5, in turn, cleave matrilin-3 and may release more matrilin-3 from the matrix, which could lead to further release of pro-inflammatory cytokines and proteases in cartilage.

Abbreviations: MMP, matrix-metalloproteinases, ADAMTS, a disintegrin and MMP with thrombospondin motifs, PHCs, primary human chondrocytes, MAPK, mitogen-activated protein kinase, ERK, extracellular signal-regulated kinase, JNK, c-Jun NH2-terminal kinase, LPS, lipopolysaccharide