Cytokine synergy, collagenases and cartilage collagen breakdown.
We have investigated proteinases that degrade cartilage collagen. We show that pro-inflammatory cytokines act synergistically with oncastatin M to promote cartilage collagen resorption by the up-regulation and activation of matrix metalloproteinases (MMPs). The precise mechanisms are not known, but involve the up-regulation of c-fos, which binds to MMP promoters at a proximal activator protein-1 (AP-1) site. This markedly up-regulates transcription and leads to higher levels of active MMP proteins.
Cawston
Tim E
TE
School of Clinical and Medical Sciences, Medical School University of Newcastle Upon Tyne, Framlington Place, Newcastle Upon Tyne NE2 4HH, U.K. T.E.Cawston@ncl.ac.uk
Milner
Jenny M
JM
Catterall
Jon B
JB
Rowan
Andrew D
AD
D000818:Animals; D002356:Cartilage / Q000201:enzymology / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism*; D017364:Collagenases / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D006868:Hydrolysis; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors / Q000494:pharmacology
D016207:Cytokines; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D003094:Collagen; D017364:Collagenases