Title
Defective collagen crosslinking in bone, but not in ligament or cartilage, in bruck syndrome: Indications for a bone-specific telopeptide lysyl hydroxylase on chromosome 17
Author
Bank, R.A.
Robins, S.P.
Wijmenga, C.
Breslau-Siderius, L.J.
Bardoel, A.F.J.
van der Sluijs, H.A.
Pruijs, H.E.H.
Tekoppele, J.M.
Publication year
1999
Abstract
Bruck syndrome is characterized by the presence of osteoporosis, joint contractures, fragile bones, and short stature. We report that lysine residues within the telopeptides of collagen type I in bone are underhydroxylated, leading to aberrant crosslinking, but that the lysine residues in the triple helix are normally modified. In contrast to bone, cartilage and ligament show unaltered telopeptide hydroxylation as evidenced by normal patterns of crosslinking. The results provide compelling evidence that collagen crosslinking is regulated primarily by tissue-specific enzymes that hydroxylate only telopeptide lysine residues and not those destined for the helical portion of the molecule. This new family of enzymes appears to provide the primary regulation for controlling the different pathways of collagen crosslinking and explains why crosslink patterns are tissue specific and not related to a genetic collagen type. A genome screen identified only a single region on chromosome 17p12 where all affected sibs shared a cluster of haplotypes identical by descent; this might be the BS (Bruck syndrome) locus and consequently the region where bone telopeptidyl lysyl hydroxylase is located. Further knowledge of this enzyme has important implications for conditions where aberrant expression of telopeptide lysyl hydroxylase occurs, such as fibrosis and scar formation.
Subject
Health Biology
Biomedical Research
peptide
procollagen lysine 2 oxoglutarate 5 dioxygenase
article
articular cartilage
chromosome 17
collagen synthesis
cross linking
enzyme regulation
human
human tissue
hydroxylation
joint contracture
mechanical stress
mineralization
osteogenesis imperfecta
osteoporosis
priority journal
scar formation
short stature
tissue specificity
Adolescent
Bone and Bones
Bone Diseases
Child
Child, Preschool
Chromosome Mapping
Chromosomes, Human, Pair 17
Collagen
Collagen Type I
Consanguinity
Contracture
Female
Genetic Markers
Genome, Human
Genotype
Growth Disorders
Homozygote
Humans
Ligaments
Male
Osteoporosis
Pedigree
Peptides
Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase
Syndrome
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DOI
https://doi.org/10.1073/pnas.96.3.1054
TNO identifier
234936
ISSN
0027-8424
Source
Proceedings of the National Academy of Sciences of the United States of America, 96 (3), 1054-1058
Document type
article