| Project/Area Number |
17591941
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Functional basic dentistry
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| Research Institution | Saga University |
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Principal Investigator |
KUKITA Akiko Saga University, Medicine, Associate Professor, 医学部, 助教授 (30153266)
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| Co-Investigator(Kenkyū-buntansha) |
KUKITA Toshio Kyushu University, Dentistry, Professor, 大学院・歯学研究院, 教授 (70150464)
SHOBUIKE Takeo Saga University, Medicine, Assistant Professor, 医学部, 助手 (70336113)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | osteoclast / transcriptional factor / transgenic mouse / 転写制御因子 / カテプシンK |
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| Research Abstract |
The OCZF gene product is a member of POK protein family that contains two domains of POZ/BTB and zinc finger in their N-and C-terminal region respectively, and that is shown to be involved in various cellular processes. Suppression of OCZF by antisense RNA inhibits osteoclast differentiation in vitro, indicating that OCZF is involved in osteoclastogenesis, but in vivo role in the process is not clear. To this end we generated transgenic mice, which expressed OCZF under the control of mouse cathepsin K promoter (Ctsk-OCZF). Nine transgenic mice were identified among the offspring by PCR and Southern blot analysis of mouse tail genomic DNA. Transgene expression was verified by RT-PCR using osteoclasts differentiated in vitro from bone marrow at 10 weeks of age. Two lines of the transgenic animals exhibited relatively high transgene expression, and were further investigated. Micro-CT and peripheral quantitative CT (pQCT) analyses and histomorphometry of femur were performed in mice at 6 weeks of age. Micro-CT imaging demonstrates a reduction in trabecular bone volume in the transgenic mice relative to normal littermates. pQCT analyses also demonstrate a reduction in bone mineral density and bone mineral content especially in trabecular bone with a decrease in strength strain index, whereas those in cortical bone were slightly affected. Consistently, von Kossa staining shows a smaller mineralized area in the transgenic mice than in normal littermates. Histological analyses with tartrate-resistant acid phosphatase staining and calcein labeling indicate an increase in the number of osteoclast, whereas bone formation rate did not significantly change. These data suggest that OCZF/LRF has an important role in osteoclastogenesis in vivo.
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