Not on its own. In healthy ankle cartilage from 30 donors aged 16 to 75, all four collagen-cutting enzymes were present but did not change with age. What age changed was the response: cartilage cells from older donors made significantly more MMP13 when provoked with an inflammatory messenger or matrix protein fragments.
Aurich and colleagues studied ankle cartilage that looked normal, taken from 30 donors aged 16 to 75, to separate ageing from disease. They measured new type II collagen being made, collagen cut by collagenases, damaged collagen, proteoglycan, and the four collagenases themselves (Aurich 2002).
The collagenases were all detectable and showed no identifiable change with age. Type II collagen and proteoglycan content didn't change after age 30. Synthesis and breakdown of type II collagen were maintained at a steady state throughout life (Aurich 2002).
There was one shift. Collagen cut by collagenase showed a trend to rise with age, and the ratio of cut to damaged collagen was positively linked to age (Aurich 2002). The authors still concluded there was no evidence in ageing ankle cartilage of the molecular degeneration seen in diseased joints.
Forsyth and colleagues asked a different question in 2005. Instead of measuring what cartilage holds at rest, they provoked isolated human cartilage cells and measured how much MMP13 the cells made in response. They used two triggers, the inflammatory messenger IL-1 beta and fragments of fibronectin, a protein in the cartilage matrix (Forsyth 2005).
They found a significant rise in MMP13 production with donor age. Even without any trigger, cells from older donors made more IL-1 beta, an inflammatory messenger that is itself under NF-kB control. Blocking NF-kB stopped the fibronectin fragments raising MMP13 (Forsyth 2005). The authors described this as an age-related increase in the cells' catabolic, or breaking-down, responsiveness.
Richard Loeser, senior author of that 2005 study, describes the shift across the ageing joint more broadly.
The cartilage becomes more brittle with age, and then the cells within the joint tissues, cartilage, meniscus, synovium, as the cells age they start to produce more inflammatory factors, and those inflammatory factors play a role in the breakdown of the tissue.
Read side by side, the two studies say that older cartilage doesn't switch MMP13 on by itself, but it is easier to tip. A knock, inflammation or one of the other triggers studied in human cartilage cells gets a bigger MMP13 response from an older cell (Aurich 2002; Forsyth 2005).
The ageing collagen itself also changes. Cartilage collagen collects sugar-derived compounds called advanced glycation end products with age, faster than skin collagen does, because it is replaced so slowly (Verzijl 2000).
Tonia Vincent was asked whether osteoarthritis is simply a consequence of getting older.
There's the biology, because we know that as we get older our repair responses are reduced. We know that the cell response to mechanical injury is also radically different. So I think all of those things confer this increased risk as we get older, but it's not inevitable.
Cartilage cells keep their own circadian clock. In cells from damaged cartilage, the clock gene PER2 ran higher and BMAL1 lower than in healthy cells, and turning BMAL1 down in healthy cells raised MMP13 (Snelling 2016). An Auckland study found that IL-1 beta, hydrogen peroxide and calcium phosphate crystals each unsettled the clock and raised MMP13, and that turning PER2 down partly reversed those changes (Rong 2019). These studies didn't test age directly, but they add another way the cell's response can be shifted.
Both key studies used cartilage cells or tissue taken from donors. The Forsyth abstract doesn't give the donors' ages or numbers, and neither study followed people over time. They show how cartilage and its cells behave at different ages, not what happens inside any one person's joint as they get older.
One 2005 study pointed to NF-kB, a switch inside cells. Blocking it stopped one of the triggers raising MMP13, and older cells made more of the NF-kB-controlled messenger IL-1 beta even at rest.
No study here shows that. Healthy ankle cartilage from donors up to 75 showed no molecular signs of degeneration with age.
Two triggers: the inflammatory messenger IL-1 beta, and fragments of fibronectin, a protein in the cartilage matrix.
For cartilage, wear and tear is an incomplete picture. Cartilage is broken down by enzymes its own cells make, chiefly MMP13 for the collagen. Healthy cartilage from...
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...
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...
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...