Defective collagen fibril formation and mineralization in osteogenesis imperfecta with congenital joint contractures (Bruck syndrome)

Brenner, Rolf E.; Vetter, U.; Stöß, H; Müller, P. K.; Teller, W. M.

doi:10.1007/bf01955060

Cited by 51 publications

(36 citation statements)

References 12 publications

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“…Indeed, inhibition of crosslinking with lathyritic agents results in decreased mineral density of bone (38). It is therefore not surprising that in BS bone, in view of the almost complete absence of HP and LP, a reduction of mineral in relation to the organic matrix is seen, as well as an aberrant size of the apatite crystals (23). The bone brittleness observed in BS is most likely caused by a combination of diminished crosslinking of the telopeptide Hyl route and defective mineralization.…”

Section: Discussionmentioning

confidence: 99%

“…Worldwide only nine families (comprising 14 patients) have been reported (22-27). Although an abnormality in the bone collagen network in BS was assumed, the underlying defect remained unknown: collagen in bone and the collagen synthesized by cultured skin fibroblasts showed none of the changes commonly found in osteogenesis imperfecta (23,(26)(27)). Here we report that the molecular defect underlying BS is a deficiency of bone-specific TLH, which results in aberrant crosslinking of bone collagen.…”

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confidence: 99%

“…Patients with BS are characterized by fragile bones with congenital joint contractures. A reduction of mineral content and an increase in size of the hydroxyapatite crystals were observed (23). Worldwide only nine families (comprising 14 patients) have been reported (22)(23)(24)(25)(26)(27).…”

mentioning

confidence: 99%

“…A reduction of mineral content and an increase in size of the hydroxyapatite crystals were observed (23). Worldwide only nine families (comprising 14 patients) have been reported (22)(23)(24)(25)(26)(27). Although an abnormality in the bone collagen network in BS was assumed, the underlying defect remained unknown: collagen in bone and the collagen synthesized by cultured skin fibroblasts showed none of the changes commonly found in osteogenesis imperfecta (23,(26)(27).…”

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confidence: 99%

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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

Bank

Robins

Wijmenga

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

178

165

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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.Collagen fibrils are important for the mechanical strength of bone (1-2). The tensile properties of fibrils result from intermolecular crosslinks connecting the nonhelical ends of a collagen molecule (telopeptides) with the triple helical part of an adjacent molecule (2-3). More than ten different collagen crosslinks are known; their structure, number, and location are highly tissue specific and not related to a specific collagen type (4-8). Stereochemical and x-ray diffraction studies revealed that differences in molecular packing of collagen within fibrils are associated with differences in crosslink profiles (9-12). Proper mineralization probably depends on a correct alignment of collagen molecules, as nucleation of calcium apatite crystals starts in the gap region, i.e., in the area adjacent to the crosslink site (9). Alterations in crosslink patterns associated with changes in the molecular packing are, therefore, expected to result in aberrant mineralization.Residues involved in crosslinking are mainly the amino acids lysine (Lys) or hydroxylysine (Hyl) (4-8). The enzyme lysyl hydroxylase (LH) (procollagen-lysine, 2-oxoglutarate 5-dioxygenase; EC 1.14.11.4) catalyzes the conversion of Lys into Hyl (13-15). Crosslinking is initiated only after specific Lys or Hyl residues of the telopeptides are converted extracellularly by the enzyme lysyl oxidase into the aldehydes allysine and hydroxyallysine, respectively (4-8). The aldehydes subsequently react with Lys, Hyl, or histidyl, residues of the triple helix to give characteristic di-, tri-, and tetrafunctional crosslinks. Two related routes for the formation of crosslinks have been described, based on ...

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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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

Bank

Robins

Wijmenga

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

178

165

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“…al. 10 performed the electron microscopy of the bone specimen of aff ected patient which showed the presence of osteoblasts with swollen mitochondria and dilated endoplasmic reticulum. They also noted a decrease in the diameter of the collagen fi brils along with low mineral content and increased pepsin extraction of collagen 1.…”

Section: Discussionmentioning

confidence: 99%

Bruck Syndrome: A Rare Disorder in New-Born with Fractures and Contractures

Dhaubhadel

Baniya

Joshi

et al. 2018

J. Nepal Paedtr. Soc.

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Bruck syndrome is a very rare autosomal recessive syndrome consisting of bone fragility and congenital joint contractures.It is considered as a combination of arthrogryposis multiplex congenita and osteogenesis imperfecta, while some consider it as the autosomal recessive variant of osteogenesis imperfecta. According to the genotype, it has been classified into types 1 and 2. To our knowledge, only about 28 patients of this syndrome have been reported so far worldwide with none been reported from Nepal. Here, we present a patient with generalized osteopenia, bilateral femur fracture and congenital joint contractures of distal extremities.

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Bruck syndrome (osteogenesis imperfecta with congenital joint contractures): Review and report on the first North American case

McPherson

Clemens

1997

Am. J. Med. Genet.

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We describe a patient who was born with flexion contractures and pterygia at the elbows, clubfeet, torticollis, and several rib fractures. During infancy and childhood, multiple fractures of the lower limbs occurred with minimal trauma and led to disabling deformities. When evaluated at age 19 years, he was normally intelligent, but extremely short, with severe kyphoscoliosis compromising his pulmonary function. Pterygia limited elbow extension to 90 degrees, and severe lower limb deformities prevented ambulation. He did not have blue sclerae, dentinogenesis imperfecta, or hearing loss. X-ray studies showed demineralized bones, severe deformity and cystic change at old fracture sites, and vertebral wedging. Collagen studies on skin fibroblasts were normal.

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Defective collagen fibril formation and mineralization in osteogenesis imperfecta with congenital joint contractures (Bruck syndrome)

Cited by 51 publications

References 12 publications

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

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

Bruck Syndrome: A Rare Disorder in New-Born with Fractures and Contractures

Bruck syndrome (osteogenesis imperfecta with congenital joint contractures): Review and report on the first North American case

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