This 2011 review explains why MMP13 became a drug target. It describes aggrecan loss as early and reversible but type II collagen loss as irreversible, calls MMP13 the major collagenase in osteoarthritic cartilage with the highest activity against type II collagen, and surveys selective MMP13 inhibitors developed since the late 1990s.
This is a review, not a new experiment. The authors gathered published work on MMP13 and on compounds designed to block it: small synthetic molecules that bind the enzyme's zinc site, molecules that block it without binding zinc, and dual inhibitors that also block aggrecanases. They paid particular attention to how lead compounds are found and how a molecule's structure relates to its activity.
The review summarises cartilage breakdown as involving two main components, type II collagen and aggrecan. Aggrecan loss is thought to be early and reversible, while type II collagen loss is considered irreversible and a key step in cartilage losing its structure and function. It states that MMP13 is specifically expressed in the cartilage of people with osteoarthritis, is not present in normal adult cartilage, is the major collagenase there and has the highest activity against type II collagen. Broad MMP inhibitors tested in people were held back by musculoskeletal side effects that depended on dose and duration, which is why selective MMP13 inhibition looks attractive.
A review summarises other people's findings and adds no new data. The statement that MMP13 is absent from normal adult cartilage is the authors' summary; Aurich 2002, for example, detected all four collagenases in healthy ankle cartilage. The review is about drug design, so it says nothing about nutrients, and the abstract does not report any selective MMP13 inhibitor succeeding in people.
This review is the clearest statement of the idea behind MMP13 research: aggrecan can recover, type II collagen cannot, and MMP13 is the enzyme best at cutting that collagen. It also explains why the target narrowed from all MMPs to MMP13 alone, after broad blockers caused side effects.
Because it acts at the step reviews call irreversible. MMP13 is the main enzyme cutting type II collagen in damaged cartilage, and that collagen renews very slowly. Mice...
It depends which part is damaged. Reviews describe losing aggrecan, the water-holding molecule in cartilage, as an early and reversible step, and losing type II collagen...
MMP13, short for matrix metalloproteinase-13 and also called collagenase-3, is an enzyme that cuts collagen. Cartilage cells make it, and of the collagen-cutting enzymes...
They attack different parts of cartilage. MMP13 is the main enzyme that cuts type II collagen, the fibre network. ADAMTS5 is the main aggrecanase, cutting aggrecan, the...