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.
Cytokine synergy, collagenases and cartilage collagen breakdown
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Jeremy Saklatvala, Hideaki Nagase, Guy Salvesen, Tim E. Cawston, Jenny M. Milner, Jon B. Catterall, Andrew D. Rowan; Cytokine synergy, collagenases and cartilage collagen breakdown. Biochem Soc Symp 1 September 2003; 70 125–133. doi: https://doi.org/10.1042/bss0700125
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