Journal
HISTOCHEMISTRY AND CELL BIOLOGY
Volume 136, Issue 1, Pages 47-56Publisher
SPRINGER
DOI: 10.1007/s00418-011-0823-1
Keywords
Bone histomorphometry; Goldner's trichrome; Osteoblasts; Osteoclasts; Osteoporosis; Thalassemia
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Funding
- Faculty of Science, Mahidol University [SCY52-02]
- Royal Golden Jubilee Program [PHD/0352/2550]
- Office of the Higher Education Commission
- Mahidol University under the National Research University Initiative
- National Science and Technology Development Agency
- Thailand Research Fund
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beta-thalassemia caused by the C -> T mutation at nucleotide 654 of the intron 2 (beta(IVSII-654)) results in aberrant splicing of beta-globin RNA, leading to an almost absence of beta-globin synthesis. Although trabecular and cortical bone loss was previously reported in beta-thalassemic mice with deletion of beta-globin gene, the microscopic changes in trabecular structure in beta(IVSII-654) thalassemic mice remained elusive. Here, we investigated the macroscopic and microscopic bone changes in 12-week-old beta(IVSII-654) knockin thalassemic mice by dual-energy X-ray absorptiometry (DXA) and histomorphometric analysis, respectively. DXA revealed a decrease in bone mineral density in the lumbar vertebrae and tibial metaphysis, but not in the femoral diaphysis, suggesting that beta(IVSII-654) thalassemia predominantly led to osteopenia at the trabecular site, but not the cortical site. Further histomorphometric analysis of the tibial secondary spongiosa showed that trabecular bone volume was significantly decreased with the expansion of marrow cavity. Decreases in osteoblast surface, osteoid surface, mineral apposition rate, mineralizing surface, and mineralized volume were also observed. Moreover, trabecular bone resorption was markedly enhanced as indicated by increases in the osteoclast surface and eroded surface. It could be concluded that beta(IVSII-654) thalassemia impaired bone formation and enhanced bone resorption, thereby leading to osteopenia especially at the trabecular sites, such as the tibial metaphysis.
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