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.
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
Tim E
TE
Cawston
Jenny M
JM
Milner
Jon B
JB
Catterall
Andrew D
AD
Rowan
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