Matrilin-3 activates the expression of osteoarthritis-associated genes in primary human chondrocytes.
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.
Klatt
Andreas R
AR
Institute for Clinical Chemistry, University of Cologne, Germany. andreas.klatt@uk-koeln.de
Klinger
Gabriele
G
Paul-Klausch
Brigitte
B
Kühn
Gertrud
G
Renno
Joerg H
JH
Wagener
Raimund
R
Paulsson
Mats
M
Schmidt
Joachim
J
Malchau
Gebhart
G
Wielckens
Klaus
K
D051722:ADAM Proteins / Q000378:metabolism; D000071121:ADAMTS4 Protein; D000071116:ADAMTS5 Protein; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D015151:Immunoblotting; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics; D016209:Interleukin-8 / Q000378:metabolism; D064235:Matrilin Proteins; D020781:Matrix Metalloproteinase 1 / Q000235:genetics; D053509:Matrix Metalloproteinase 13 / Q000235:genetics; D019278:Matrix Metalloproteinase 3 / Q000235:genetics; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D010003:Osteoarthritis / Q000235:genetics*; D011348:Procollagen N-Endopeptidase / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016326:Extracellular Matrix Proteins; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D064235:Matrilin Proteins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D051722:ADAM Proteins; D000071116:ADAMTS5 Protein; C121532:ADAMTS5 protein, human; D053509:Matrix Metalloproteinase 13; D011348:Procollagen N-Endopeptidase; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1; D000071121:ADAMTS4 Protein; C000603918:ADAMTS4 protein, human