This 2000 lab study worked out how interleukin-1 (IL-1), an inflammatory signal, switches on the MMP13 gene in cartilage cells. It needed p38, JNK and NF-kB all together. MMP-1, a related collagenase, was switched on through different pathways, which also varied between cell types.
Researchers treated cultured chondrocytes with IL-1 and first checked whether it raised MMP13 by increasing gene transcription or by acting after that step. They then used direct inhibitors of the MAP kinase pathways and a permanent blocker of NF-kB to test which pathways IL-1 needed. They ran the same kind of tests for MMP-1 in articular chondrocytes and in chondrosarcoma cells.
IL-1 induction of MMP13 required p38 activity, JNK activity and the movement of NF-kB into the nucleus, which suggests both NF-kB and AP-1 transcription factors are needed. In chondrosarcoma cells, MMP-1 induction depended on p38 and MEK and did not need JNK or NF-kB. In articular chondrocytes, blocking MEK had no effect on MMP-1 and blocking p38 gave variable results. The authors say this was the first demonstration that all three are required for IL-1 to induce MMP13.
The abstract does not say which species the chondrocytes came from or how many were studied. Pathway inhibitors in a dish are blunt tools and can affect more than their target. The study shows how the switch is wired in cells, not how often IL-1 is present in a joint or how much it matters there.
NF-kB comes up again and again in MMP13 research, including in studies of curcumin, boswellia's AKBA and ageing cartilage cells. This paper is one of the foundations for that: IL-1 could not switch on MMP13 without it. It also shows MMP13 and MMP-1 are controlled differently, even though both are collagenases.
Yes, in lab studies. The inflammatory messenger IL-1 raised MMP13 in human cartilage and cartilage cells in several studies, and TNF-alpha did too. To switch the MMP13...
In human cartilage cells, MMP13 rose in response to inflammatory messengers such as IL-1, oxidative stress, calcium phosphate crystals, a disrupted cell body clock...
Both are collagenases, enzymes that can cut intact collagen, and they cut type II collagen at the same bond. MMP13 is much faster at it: at least ten times faster than...