Collagen overglycosylation: a biochemical feature that may contribute to bone quality.
Skeletal ability to resist mechanical stress is determined by bone amount and quality, which relies on macro- and micro-architecture, turnover, bone matrix, and mineralisation; the role of collagen has not been clearly elucidated. Numerous post-translational steps are involved in collagen type I biosynthesis, including residue hydroxylation and glycosylation catalysed by enzymes that work until the protein folds forming the triple helix; therefore, folding rate regulates these processes. Overglycosylated hydroxylysines are poor substrates for epsilon-amino group deamination which initiates cross-link formation. Three clinical conditions associated with fractures may relate collagen overglycosylation with bone quality: (i) Osteogenesis Imperfecta, in which genetic mutations distort triple helix conformation and slow folding rate favouring overglycosylation; (ii) diabetes mellitus, with collagen overglycosylation by AGE accumulation; and, (iii) menopause, according to experimental studies demonstrating ovariectomy-related trabecular bone collagen overglycosylation preventable by 17beta-estradiol or tamoxifen. Specific actions on collagen of drugs used for bone protection should be explored in future studies.
Dominguez
Ligia J
LJ
Geriatric Unit, University of Palermo, Palermo, Italy. mabar@unipa.it <mabar@unipa.it>
Barbagallo
Mario
M
Moro
Luigi
L
D001842:Bone and Bones / Q000378:metabolism / Q000502:physiology*; D003094:Collagen / Q000096:biosynthesis / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D010013:Osteogenesis Imperfecta / Q000235:genetics / Q000378:metabolism; D017698:Postmenopause
D003094:Collagen