In the lab, it can. University of Auckland researchers found that raising glucose from 4 to 10 mM, within the range from normal to high blood sugar, made cells from damaged knee cartilage produce more MMP13 and ADAMTS5 when oxygen was plentiful. Cells from normal-looking cartilage did not respond the same way.
Jain and colleagues took cartilage cells from damaged and from normal-looking human cartilage and kept them for 24 hours in 4, 6, 8 or 10 mM glucose, a span the authors placed within the normal blood glucose and high blood sugar range. They ran the tests twice, once at 18.9% oxygen and once at 1% (Jain 2024).
With plenty of oxygen, cells from damaged cartilage used more glucose at 10 mM than at 4 mM, carried more of the GLUT1 glucose transporter, and made more MMP13 and ADAMTS5, at both the gene and protein level. Cells from normal-looking cartilage didn't show those rises (Jain 2024).
At 1% oxygen, the extra glucose made no difference to MMP13 or ADAMTS5 (Jain 2024).
Cartilage has no even oxygen supply. The same Auckland group describes about 6% oxygen as matching the surface zone of cartilage in the body and about 1% as matching the deep zone (Jain 2023). In their 2023 study, cells from damaged cartilage made more MMP13 than cells from normal-looking cartilage at higher oxygen levels but not at low oxygen, and the authors noted an earlier finding that oxygen levels are raised in damaged cartilage in the body (Jain 2023).
So the glucose effect showed up in the conditions of the oxygenated surface layer. The authors suggested high blood sugar might add to cartilage breakdown in that surface zone (Jain 2024).
The link ran through RUNX2, a control protein that regulates the MMP13, ADAMTS5 and GLUT1 genes. In cells from damaged cartilage at high oxygen, RUNX2 protein rose at 10 mM glucose compared with 4 mM (Jain 2024). Cells from normal-looking cartilage had lower RUNX2 overall, and glucose had no consistent effect on it (Jain 2024).
A separate line of research looks at the collagen rather than the cells. Advanced glycation end products, or AGEs, form when sugars react with proteins. They build up with age in collagen, and faster in cartilage collagen than in skin collagen (Verzijl 2000). Verzijl and colleagues showed the difference comes mostly from turnover: cartilage collagen stays in place for so long, with an estimated half-life of 117 years, that it has more time to collect them (Verzijl 2000).
Metabolism reaches cartilage by more than glucose. In cells from normal-looking areas of cartilage, taken at knee replacement from patients who all had a body mass index over 30, leptin at 20 or 40 ng/ml lowered the cartilage-building protein SOX9 and raised ADAMTS5. MMP13 rose only at 40 ng/ml (Primrose 2023). The authors noted that joint fluid leptin at that level is typical in metabolic syndrome, in women, or both.
Tom Appleton links these molecules to the extra osteoarthritis risk that comes with obesity, including in the hands, which carry no extra weight.
Too much glucose, too many fatty acids, especially long-chain fatty acids, and hormones that are released from fat called adipokines. You've probably heard about leptin before. Leptin is a major one that's mediating obesity, also increases the risk of osteoarthritis, but there are many other mechanisms in play.
These are cell studies, measured over 24 hours in a dish. They show that glucose and leptin can shift what cartilage cells make. They don't show what blood sugar does to cartilage in people, how long it would take, or whether lowering blood sugar changes it. No study here tested that.
mM is millimoles per litre, the same unit (mmol/L) that New Zealand blood glucose readings use. The Auckland study tested 4, 6, 8 and 10 mM, a range the authors placed between normal blood glucose and high blood sugar.
No. The rise was seen in cells from damaged cartilage, and only at high oxygen. Cells from normal-looking cartilage didn't show it.
Sugar-derived compounds called AGEs build up in cartilage collagen with age, faster than in skin, because the collagen is replaced so slowly.
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...
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...
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...
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...