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

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-1beta, TNFalpha, 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-1beta. 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.

• Authors: Andreas R Klatt, Gabriele Klinger, Brigitte Paul-Klausch, Gertrud Kühn, Joerg H Renno, Raimund Wagener, Mats Paulsson, Joachim Schmidt, Gebhart Malchau, Klaus Wielckens
• Journal: FEBS letters (FEBS Lett) Vol. 583 Issue 22 Pg. 3611-7 (Nov 19 2009) ISSN: 1873-3468 [Electronic] England
• PMID: 19840795 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Extracellular Matrix Proteins
• Interleukin-1beta
• Interleukin-6
• Interleukin-8
• Matrilin Proteins
• Recombinant Proteins
• Tumor Necrosis Factor-alpha
• Nitric Oxide Synthase Type II
• Cyclooxygenase 2
• PTGS2 protein, human
• ADAM Proteins
• ADAMTS5 Protein
• ADAMTS5 protein, human
• Matrix Metalloproteinase 13
• Procollagen N-Endopeptidase
• Matrix Metalloproteinase 3
• Matrix Metalloproteinase 1
• ADAMTS4 Protein
• ADAMTS4 protein, human

Topics

• ADAM Proteins (metabolism)
• ADAMTS4 Protein
• ADAMTS5 Protein
• Cells, Cultured
• Chondrocytes (cytology, drug effects, metabolism)
• Cyclooxygenase 2 (genetics)
• Enzyme-Linked Immunosorbent Assay
• Extracellular Matrix Proteins (genetics, pharmacology)
• Gene Expression Regulation (drug effects)
• Humans
• Immunoblotting
• Interleukin-1beta (metabolism)
• Interleukin-6 (genetics)
• Interleukin-8 (metabolism)
• Matrilin Proteins
• Matrix Metalloproteinase 1 (genetics)
• Matrix Metalloproteinase 13 (genetics)
• Matrix Metalloproteinase 3 (genetics)
• Nitric Oxide Synthase Type II (genetics)
• Osteoarthritis (genetics)
• Procollagen N-Endopeptidase (metabolism)
• Recombinant Proteins (pharmacology)
• Reverse Transcriptase Polymerase Chain Reaction
• Tumor Necrosis Factor-alpha (metabolism)