Crosslinking by advanced glycation end products increases the stiffness of the collagen network in human articular cartilage: a possible mechanism through which age is a risk factor for osteoarthritis

Verzijl N, DeGroot J, Ben ZC, Brau-Benjamin O, Maroudas A, Bank RA, Mizrahi J, Schalkwijk CG, Thorpe SR, Baynes JW, Bijlsma JW, Lafeber FP, TeKoppele JM · Arthritis and Rheumatism

The paper that makes glycation a cartilage story rather than a diabetes one. Raising AGE levels produced a dose-dependent increase in collagen-network stiffness — instantaneous deformation fell by up to 40% at 200 mM threose, correlating with AGE fluorescence (r = −0.81, p < 0.0001) and confirmed by osmotic stress measurement. Glycation inhibitors attenuated the effect. Stiffer collagen resists deformation and fails sooner, which is proposed as the molecular reason age is the dominant risk factor for osteoarthritis.

Population

Human adult articular cartilage incubated with threose to raise advanced glycation end-product levels

Intervention

AGE crosslinking of the collagen network

Comparator

Untreated cartilage; co-incubation with arginine or lysine as glycation inhibitors

Limitations

Threose incubation is a laboratory accelerant, not a diet; the AGE levels reached are calibrated to aged human cartilage but arrived at in days rather than decades. It is an explant biomechanics study with no animal or human arm.