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 it has the highest activity against type II collagen, the fibre that holds joint cartilage together. That is why cartilage researchers single it out.
MMP13 is one of the matrix metalloproteinases, or MMPs, a family of enzymes that break down the proteins in the material around cells. Its protein sequence carries the family's zinc-binding site and a short stretch that keeps the enzyme switched off until it is activated (Freije 1994). Cells release it as an inactive proenzyme, and it has to be cut down to a smaller, active form before it can work (Knäuper 1996).
Within the family it belongs to the small group of collagenases, the enzymes able to cut intact collagen. When Freije and colleagues cloned it in 1994, it was the third human collagenase known, after the fibroblast and neutrophil collagenases, so they named it collagenase-3 (Freije 1994). MMP13 and collagenase-3 are two names for the same enzyme.
That first copy came from breast tumour tissue. The team found no collagenase-3 in the normal tissues they tested, which included breast, liver, placenta and prostate (Freije 1994).
Two years later, two groups showed that cartilage cells make it too. Mitchell and colleagues found MMP13 in the cartilage cells, or chondrocytes, of worn human cartilage (Mitchell 1996). Reboul and colleagues found that chondrocytes made collagenase-3 but the cells lining the joint did not, and that chondrocytes from damaged cartilage produced about 9.5 times as much of the protein as those from normal cartilage (Reboul 1996).
Collagen makes up about two-thirds of the dry mass of adult joint cartilage, and type II collagen is its main molecule (Eyre 2002). MMP13 is unusually good at cutting it. In Mitchell's experiments it broke down type II collagen at least ten times faster than MMP-1, the first collagenase described (Mitchell 1996). Purified MMP13 preferred type II collagen and was five or six times less efficient on types I and III (Knäuper 1996).
Reviews now describe MMP13 as the primary MMP involved in cartilage breakdown, picked out for its ability to cleave type II collagen (Hu 2021), and as the major collagenase in damaged cartilage, with the highest activity against type II collagen of any MMP (Li 2011).
Mike Zuscik introduced the enzyme in one line while showing MMP13 staining from a mouse joint-injury study.
If we do some immunofluorescence to evaluate MMP13 expressions, this is the enzyme that is degrading type 2 collagen in the cartilage matrix.
The papers don't fully agree on how much MMP13 healthy cartilage carries. A 2011 review describes MMP13 as specific to damaged cartilage and absent from normal adult cartilage (Li 2011). A 2002 study of healthy ankle cartilage from 30 donors aged 16 to 75 detected all four collagenases, at levels that did not change with age, while collagen stayed in a steady state (Aurich 2002).
Either way, the body has brakes. Its own inhibitors, TIMP-1, TIMP-2 and TIMP-3, each blocked active MMP13 one molecule to one in the lab (Knäuper 1996).
Frank Beier, explaining how genes are switched on and off in osteoarthritis, described the collagen-cutting enzymes this way.
In osteoarthritis we have certain genes that are being switched on that includes, for example, genes for enzymes that break down collagen and other markers. So these genes are usually not very active, but in osteoarthritis the genes are being turned on.
Two mouse experiments make the case. Mice engineered to make an always-active human MMP13 in their cartilage developed cartilage erosion and excessive cutting of type II collagen (Neuhold 2001). Mice with no MMP13 at all had less cartilage erosion eight weeks after a knee injury than normal mice (Little 2009). Because collagen loss is treated as the irreversible step in cartilage damage, MMP13 has become a target for drug developers (Li 2011).
The name MMP13 Cartilage Technology™ comes from this enzyme.
Yes. Collagenase-3 was the name its discoverers gave it in 1994, because it was the third human collagenase described. MMP13 is its number in the matrix metalloproteinase family.
Both. MMP13 is the gene, and the enzyme it codes for is usually written MMP-13 in research papers. Studies measure either the gene's activity (its mRNA) or the protein itself.
Cartilage cells, called chondrocytes. One 1996 study found chondrocytes made it but the cells lining the joint did not.
MMP13 cuts type II collagen, the rope-like fibre that gives cartilage its strength. It cleaves each three-stranded collagen molecule at one spot, leaving a three-quarter...
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...
Type II collagen is the main collagen in joint cartilage. Collagen makes up about two-thirds of adult cartilage's dry mass, and type II is its principal molecule, woven...
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...