Putative role of lysyl hydroxylation and pyridinoline cross-linking during adolescence in the occurrence of osteoarthritis at old age.
OBJECTIVE
The collagen network in human articular cartilage experiences a large number of stress cycles during life as it shows hardly any turnover after adolescence. We hypothesized that, to withstand fatigue failure, the physical condition of the collagen network laid down at adolescence is of crucial importance for the age of onset of osteoarthritis (OA).


METHODS
We have compared the lysyl hydroxylation level and pyridinoline cross-link level of the collagen network of degenerated (DG) cartilage of the femoral knee condyle (representing a preclinical early stage of OA) with that of normal cartilage from the contralateral knee. The biological age of the collagen network was determined by means of pentosidine levels. For each donor, collagen modifications of normal cartilage were compared with DG cartilage that showed no significant remodeling of the collagen network (as evidenced by identical pentosidine levels).


RESULTS
DG cartilage contained significantly more hydroxylysine residues per collagen molecule in comparison with healthy cartilage from the same donor, both in the upper and lower half (the region near the articular surface and adjacent to bone, respectively). In addition, a significantly higher level of pyridinoline cross-linking was observed in the upper half of DG cartilage. Considering the biological age of the collagen network, the changes observed in DG cartilage must have been present several decades before cartilage became degenerated.


CONCLUSIONS
The data suggest that high levels of lysyl hydroxylation and pyridinoline cross-linking result in a collagen network that fails mechanically in long term loading. Areas containing collagen with low hydroxylysine and pyridinoline levels are less prone to degeneration. As such, this study indicates that post-translational modifications of collagen molecules synthesized during adolescence are causally involved in the pathogenesis of OA.
Bank
R A
RA
Gaubius Laboratory TNO Prevention and Health, Leiden, The Netherlands. RA.Bank@pg.tno.nl
Verzijl
N
N
Lafeber
F P J G
FP
Tekoppele
J M
JM
D000368:Aged; D000369:Aged, 80 and over; D000596:Amino Acids / Q000502:physiology*; D001120:Arginine / Q000031:analogs & derivatives* / Q000032:analysis; D016022:Case-Control Studies; D003094:Collagen / Q000502:physiology*; D003432:Cross-Linking Reagents / Q000378:metabolism*; D006801:Humans; D006901:Hydroxylysine / Q000502:physiology*; D008239:Lysine / Q000031:analogs & derivatives* / Q000032:analysis; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000209:etiology*
D000596:Amino Acids; D003432:Cross-Linking Reagents; D006901:Hydroxylysine; C015484:pyridinoline; D003094:Collagen; D001120:Arginine; C062187:pentosidine; D008239:Lysine