Glycosylation of human bone collagen I in relation to lysylhydroxylation and fibril diameter

Posttranslational modifications (lysylhydroxylation, glycosylation, and crosslink formation) of collagen I and the trabecular bone volume (TBV) as well as the supramolecular organization of human vertebrae were studied by analyzing vertebral bones of 55 individuals (22-93 years of age). The degree of lysylhydroxylation of both α-chains of collagen I showed a significant inverse correlation with the TBV, while only a weak correlation between lysylhydroxylation of α2(I) and the age of the donor was observed. The degree of glycosylation of collagen I was significantly correlated with both the level of lysylhydroxylation and the degree of osteopenia. Electronmicroscopic evaluation did not show any relationship between the level of collagen glycosylation and the diameter of in vivo formed fibrils or in vitro formed fibrillar aggregates. In our study the molar ratio of the mature collagen crosslinks, pyridinoline and deoxypyridinoline, showed a slight tendency to be higher, in particular in the samples with a high level of lysylhydroxylation. This ratio was recently found to be significantly increased in avian osteoporotic bone. Our data suggest that the increased level of lysylhydroxylation in human osteopenia is related to the glycosylation of collagen I, while it seems to have little impact on the formation of the mature, non-reducible collagen crosslinks investigated. Based on our observations it appears unlikely that the different diameters of collagen fibrils contribute greatly to the reduced biomechanical stability reported for overhydroxylated, osteopenic bone tissue.