Статья

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

Ruud A. BankGaubius Laboratory TNO Prevention and Health, Division of Vascular and Connective Tissue Research, P.O. Box 2215, 2301 CE Leiden, The Netherlands; Rowett Research Institute, Skeletal Research Unit, Bucksburn, Aberdeen AB21 9SB, Scotland, United Kingdom; Department of Human Genetics, Utrecht University, P.O. Box 80030, 3508 TA Utrecht, The Netherlands; Clinical Genetics Center, P.O. Box 18009, 3501 CA Utrecht, The Netherlands; Academic Hospital Free University, Department of Orthopaedics, P.O. BoxSimon P. RobinsGaubius Laboratory TNO Prevention and Health, Division of Vascular and Connective Tissue Research, P.O. Box 2215, 2301 CE Leiden, The Netherlands; Rowett Research Institute, Skeletal Research Unit, Bucksburn, Aberdeen AB21 9SB, Scotland, United Kingdom; Department of Human Genetics, Utrecht University, P.O. Box 80030, 3508 TA Utrecht, The Netherlands; Clinical Genetics Center, P.O. Box 18009, 3501 CA Utrecht, The Netherlands; Academic Hospital Free University, Department of Orthopaedics, P.O. BoxCisca WijmengaGaubius Laboratory TNO Prevention and Health, Division of Vascular and Connective Tissue Research, P.O. Box 2215, 2301 CE Leiden, The Netherlands; Rowett Research Institute, Skeletal Research Unit, Bucksburn, Aberdeen AB21 9SB, Scotland, United Kingdom; Department of Human Genetics, Utrecht University, P.O. Box 80030, 3508 TA Utrecht, The Netherlands; Clinical Genetics Center, P.O. Box 18009, 3501 CA Utrecht, The Netherlands; Academic Hospital Free University, Department of Orthopaedics, P.O. BoxLiesbeth J. Breslau-SideriusGaubius Laboratory TNO Prevention and Health, Division of Vascular and Connective Tissue Research, P.O. Box 2215, 2301 CE Leiden, The Netherlands; Rowett Research Institute, Skeletal Research Unit, Bucksburn, Aberdeen AB21 9SB, Scotland, United Kingdom; Department of Human Genetics, Utrecht University, P.O. Box 80030, 3508 TA Utrecht, The Netherlands; Clinical Genetics Center, P.O. Box 18009, 3501 CA Utrecht, The Netherlands; Academic Hospital Free University, Department of Orthopaedics, P.O. BoxA. BardoelGaubius Laboratory TNO Prevention and Health, Division of Vascular and Connective Tissue Research, P.O. Box 2215, 2301 CE Leiden, The Netherlands; Rowett Research Institute, Skeletal Research Unit, Bucksburn, Aberdeen AB21 9SB, Scotland, United Kingdom; Department of Human Genetics, Utrecht University, P.O. Box 80030, 3508 TA Utrecht, The Netherlands; Clinical Genetics Center, P.O. Box 18009, 3501 CA Utrecht, The Netherlands; Academic Hospital Free University, Department of Orthopaedics, P.O. BoxHans A. Van der SluijsGaubius Laboratory TNO Prevention and Health, Division of Vascular and Connective Tissue Research, P.O. Box 2215, 2301 CE Leiden, The Netherlands; Rowett Research Institute, Skeletal Research Unit, Bucksburn, Aberdeen AB21 9SB, Scotland, United Kingdom; Department of Human Genetics, Utrecht University, P.O. Box 80030, 3508 TA Utrecht, The Netherlands; Clinical Genetics Center, P.O. Box 18009, 3501 CA Utrecht, The Netherlands; Academic Hospital Free University, Department of Orthopaedics, P.O. BoxHans E. H. PruijsGaubius Laboratory TNO Prevention and Health, Division of Vascular and Connective Tissue Research, P.O. Box 2215, 2301 CE Leiden, The Netherlands; Rowett Research Institute, Skeletal Research Unit, Bucksburn, Aberdeen AB21 9SB, Scotland, United Kingdom; Department of Human Genetics, Utrecht University, P.O. Box 80030, 3508 TA Utrecht, The Netherlands; Clinical Genetics Center, P.O. Box 18009, 3501 CA Utrecht, The Netherlands; Academic Hospital Free University, Department of Orthopaedics, P.O. BoxJohan M. TeKoppeleGaubius Laboratory TNO Prevention and Health, Division of Vascular and Connective Tissue Research, P.O. Box 2215, 2301 CE Leiden, The Netherlands; Rowett Research Institute, Skeletal Research Unit, Bucksburn, Aberdeen AB21 9SB, Scotland, United Kingdom; Department of Human Genetics, Utrecht University, P.O. Box 80030, 3508 TA Utrecht, The Netherlands; Clinical Genetics Center, P.O. Box 18009, 3501 CA Utrecht, The Netherlands; Academic Hospital Free University, Department of Orthopaedics, P.O. Box

1999en

ABI

Аннотация

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.

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Идентификаторы

DOI: 10.1073/pnas.96.3.1054

Цитирования и источники

Цитирований: 2Использованных источников: 0

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