Type V OI primary osteoblasts display increased mineralization despite decreased COL1A1 expression.
J Clin Endocrinol Metab
; 100(2): E325-32, 2015 Feb.
Article
em En
| MEDLINE
| ID: mdl-25387264
ABSTRACT
CONTEXT Patients with type V osteogenesis imperfecta (OI) are heterozygous for a dominant IFITM5 c.-14C>T mutation, which adds five residues to the N terminus of bone-restricted interferon-induced transmembrane-like protein (BRIL), a transmembrane protein expressed in osteoblasts. Type V OI skeletal findings include hyperplastic callus formation, ossification of the forearm interosseous membrane, and dense metaphyseal bands. OBJECTIVE:
The objective of this study was to examine the role of osteoblasts in the active mineralization traits of type V OI and the effect of the IFITM5 mutation on type I collagen.METHODS:
We identified eight patients with the IFITM5 c.-14C>T mutation. Cultured osteoblasts from type V OI patients were used to study osteoblast differentiation and mineralization.RESULTS:
We verified the expression and stability of mutant IFITM5 transcripts. In differentiated type V OI primary osteoblasts in culture, the IFITM5 expression and BRIL level is comparable with control. Both early and late markers of osteoblast differentiation are increased in type V OI osteoblasts. Mineralization, assayed by alizarin red staining, was increased in type V OI osteoblasts compared with control. However, type V OI osteoblasts have significantly decreased COL1A1 transcripts in mid- to late differentiation. Type I collagen protein is concomitantly decreased, with decreased cross-linked collagen in matrix and altered appearance of fibrils deposited in culture.CONCLUSIONS:
This study demonstrates that type V OI mineralization has a gain-of-function mechanism at the osteoblast level, which likely underlies the overactive tissue mineralization seen in patients. Decreased type I collagen expression, secretion, and matrix incorporation establish type V OI as a collagen-related defect.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Osteoblastos
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Osteogênese Imperfeita
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Calcinose
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Colágeno Tipo I
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Proteínas de Membrana
Tipo de estudo:
Prognostic_studies
Limite:
Adult
/
Aged
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Child, preschool
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Clin Endocrinol Metab
Ano de publicação:
2015
Tipo de documento:
Article