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-translationalsteps are involved in collagen type I biosynthesis, including residue hydroxylation and glycosylation catalysed by enzymes that workuntil the protein folds forming the triple helix; therefore, folding rate regulates these processes. Overglycosylated hydroxylysines arepoor substrates for e-amino group deamination which initiates cross-link formation. Three clinical conditions associated with fracturesmay relate collagen overglycosylation with bone quality: (i) Osteogenesis Imperfecta, in which genetic mutations distort triplehelix conformation and slow folding rate favouring overglycosylation; (ii) diabetes mellitus, with collagen overglycosylation by AGEaccumulation; and, (iii) menopause, according to experimental studies demonstrating ovariectomy-related trabecular bone collagenoverglycosylation preventable by 17b-estradiol or tamoxifen. Specific actions on collagen of drugs used for bone protection shouldbe explored in future studies.
|Journal||Biochemical and Biophysical Research Communications|
|Publication status||Published - 2005|
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology