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Matrilin‐3 activates the expression of osteoarthritis‐associated genes in primary human chondrocytes
Author(s) -
Klatt Andreas R.,
Klinger Gabriele,
Paul-Klausch Brigitte,
Kühn Gertrud,
Renno Joerg H.,
Wagener Raimund,
Paulsson Mats,
Schmidt Joachim,
Malchau Gebhart,
Wielckens Klaus
Publication year - 2009
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2009.10.035
Subject(s) - mmp3 , proteases , chemistry , microbiology and biotechnology , mmp1 , cartilage , matrix metalloproteinase , osteoarthritis , in vitro , tumor necrosis factor alpha , stimulation , extracellular matrix , proinflammatory cytokine , gene expression , gene , immunology , inflammation , anatomy , biology , biochemistry , medicine , enzyme , pathology , endocrinology , alternative medicine
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.