Bone microstructural defects and osteopenia in hemizygous ßIVSII-654 knockin thalassemic mice: sex-dependent changes in bone density and osteoclast function.
Am J Physiol Endocrinol Metab
; 309(11): E936-48, 2015 Dec 01.
Article
em En
| MEDLINE
| ID: mdl-26487004
ABSTRACT
ß-Thalassemia, a hereditary anemic disorder, is often associated with skeletal complications that can be found in both males and females. The present study aimed to investigate the age- and sex-dependent changes in bone mineral density (BMD) and trabecular microstructure in ß(IVSII-654) knockin thalassemic mice. Dual-energy X-ray absorptiometry and computer-assisted bone histomorphometry were employed to investigate temporal changes in BMD and histomorphometric parameters in male and female mice of a ß(IVSII-654) knockin mouse model of human ß-thalassemia, in which impaired splicing of ß-globin transcript was caused by hemizygous CâT mutation at nucleotide 654 of intron 2. Young, growing ß(IVSII-654) mice (1 mo old) manifested shorter bone length and lower BMD than their wild-type littermates, indicating possible growth retardation and osteopenia, the latter of which persisted until 8 mo of age (adult mice). Interestingly, two-way analysis of variance suggested an interaction between sex and ß(IVSII-654) genotype, i.e., more severe osteopenia in adult female mice. Bone histomorphometry further suggested that low trabecular bone volume in male ß(IVSII-654) mice, particularly during a growing period (1-2 mo), was primarily due to suppression of bone formation, whereas both a low bone formation rate and a marked increase in osteoclast surface were observed in female ß(IVSII-654) mice. In conclusion, osteopenia and trabecular microstructural defects were present in both male and female ß(IVSII-654) knockin thalassemic mice, but the severity, disease progression, and cellular mechanism differed between the sexes.
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Base de dados:
MEDLINE
Assunto principal:
Osteoclastos
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Osteoporose
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Osso e Ossos
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Envelhecimento
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Talassemia beta
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article