Bone microstructural defects and osteopenia in hemizygous [[beta].sup.IVSII- 654] knockin thalassemic mice: sex-dependent changes in bone density and osteoclast function

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Publisher: American Physiological Society
Document Type: Author abstract; Report
Length: 241 words

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Abstract :

[beta]-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 [[beta].sup.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 [[beta].sup.IVSII-654] knockin mouse model of human [beta]-thalassemia, in which impaired splicing of [beta]-globin transcript was caused by hemizygous C[right arrow]T mutation at nucleotide 654 of intron 2. Young, growing [[beta].sup.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 [[beta].sup.IVSII- 654] genotype, i.e., more severe osteopenia in adult female mice. Bone histomorphometry further suggested that low trabecular bone volume in male [[beta].sup.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 [[beta].sup.IVSII-654] mice. In conclusion, osteopenia and trabecular microstructural defects were present in both male and female [[beta].sup.IVSII-654] knockin thalassemic mice, but the severity, disease progression, and cellular mechanism differed between the sexes. [beta]-thalassemia; bone histomorphometry; bone mineral density; osteoporosis doi: 10.1152/ajpendo.00416.2015.

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Gale Document Number: GALE|A442285746