| Project/Area Number |
26670028
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Biological pharmacy
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| Research Institution | National Institute of Health Sciences |
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Principal Investigator |
Yamazaki Daiju 国立医薬品食品衛生研究所, 薬理部, 主任研究官 (40467428)
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| Co-Investigator(Kenkyū-buntansha) |
KOMAZAKI Shinji 埼玉医科大学, 解剖学, 准教授 (80129155)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | TRICチャネル / 骨芽細胞 / 破骨細胞 / 骨形成不全症 |
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| Outline of Final Research Achievements |
Deletion and point mutations in TRIC-B occur in autosomal recessive osteogenesis imperfecta pedigrees. Tric-b-knockout mice develop neonatal respiratory failure and exhibit poor bone ossification. We found that bones from the knockout mice contained bone-related cells preserving regular histological features, but collagen matrix deposition was reduced. Osteoblasts, the bone-depositing cells, from Tric-b-knockout mice exhibited reduced Ca2+ release from the ER and increased store Ca2+ contents, which was associated with ER swelling. These cells also had impaired collagen production without a decrease in collagen-encoding transcripts, consistent with a defect in trafficking of collagen through the ER. In contrast, osteoclasts, the bone-degrading cells, from Tric-b-knockout mice were comparable to those from wild-type mice. Thus, TRIC-B function is essential to support the large amount of collagen that active osteoblasts produce to enable bone mineralization.
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