Possible role of overglycosylation in the type I collagen triple helical domain in the molecular pathogenesis of osteogenesis imperfecta

Abstract

The underlying defect in patients affected by a form of osteogenesis imperfecta (OI) clarified at the molecular level regards the amount or the structure of type I collagen synthesized. This leads to a decreased and/or abnormal mineral deposition in bone and affects bone mass and/or strength. Abnormal interactions between collagen molecules in the presence of mutant trimers could give rise to abnormal fibrils, which, in turn, can determine incorrect interactions with noncollagenous matrix macromolecules. The interactious can be disturbed or modulated by an abnormal distribution on the collagen fibril surface of electrically charged or hydrophobic groups, or by an increased presence of sugar moieties linked to hydroxylysyl residues due to chain post‐translational overmodifications (lysyl overhydroxylation and hydroxylysyl over‐glycosylation) of the portion of the triple helical domain of abnormal type I collagen molecules N‐terminal with respect to the defect localization.