Role of novel transcription factor on bone formation
| Project/Area Number |
18592032
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|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Functional basic dentistry
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|---|
| Research Institution | Osaka University |
|---|
Principal Investigator |
KAWAI Shinji Osaka University, Graduate school of dentistry, Assistant professor (40362678)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
AMANO Atsuo Osaka University, Graduate School of Dentistry, Professor (50193024)
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|---|
| Project Period (FY) |
2006 – 2007
|
| Project Status |
Completed (Fiscal Year 2007)
|
| Budget Amount *help |
¥3,820,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2006: ¥2,000,000 (Direct Cost: ¥2,000,000)
|
|---|
| Keywords | Osteoblast / Differentiation / Tramsgenic mice / Transcription factor / Bone formation / Microarray |
|---|
| Research Abstract |
We report that Osr2 is one of the regulators of osteoblast function, since dominant-negative Osr2 transgenic mice exhibited decreased osteoblast activity, as well as delayed mineralization in calvarial and tibial bone tissues. Our results indicate that Osr2 functions in regulation of osteoblast proliferation. Molecular mechanisms that control bone formation have received attention with increasing knowledge related to genetic control of osteoblast differentiation. The odd-skipped related (Osr) gene is a zinc-finger transcription factor recently suggested to be involved in bone formation, though little is known about its role. To elucidate the in vivo function of Osr2, we generated transgenic mice overexpressing dominant-negative Osr2. In the present study, N-terminal deleted Osr2 was found to act as a dominant-negative mutant toward both Osr1 and Osr2. Dominant-negative Osr2 (Osr2ΔN) transgenic mice demonstrated delayed mineralization in calvarial and cortical bone tissues. Further, soft X-ray analysis of transgenic mice bones revealed distinctly increased radiolucency. Examinations of newborn Osr2ΔN transgenic mice skeletons stained with alcian blue and alizarin red showed reduced intensities in the skull and skeletal elements. Morphologically, calvaria and tibia of Osr2ΔN transgenic mice were composed of markedly thinner parietal and cortical bones, and lower numbers of osteoblastic cells on bone surfaces, indicating a reduced proliferation of osteoblasts. Further, calvarial osteoblasts obtained from Osr2ΔN transgenic mice showed highly attenuated osteoblast differentiation and proliferation, confirming that Osr2 is required for osteogenesis. Finally, results of Runx2-deficient cell assays suggested that Osr2 induces ALP expression, but to a lesser degree than Runx2-expressing cells. Our genetic observations showed that the Osr2 gene plays a key role in osteoblastic cell proliferation.
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Report
(3 results)
Research Products
(95 results)
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[Book] 歯科医学の最先端2008
Author(s)
天野敦雄, 他4名(分担)
Total Pages
321
Publisher
大阪大学出版会
Description
「研究成果報告書概要(和文)」より
Related Report
