| Project/Area Number |
16390524
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Morphological basic dentistry
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| Research Institution | Niigata University |
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Principal Investigator |
AMIZUKA Norio Niigata University, Center for Transdisciplinary Research, professor, 超域研究機構, 教授 (30242431)
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| Co-Investigator(Kenkyū-buntansha) |
MAEDA Takeyasu Niigata University, Institute of Medicine and Dentistry, professor, 医歯学系, 教授 (40183941)
OZAWA Hidehiro Matsumoto Dental University, Graduate School of Oral Medicine, professor, 大学院・歯学独立研究科, 教授 (60018413)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥14,600,000 (Direct Cost: ¥14,600,000)
Fiscal Year 2005: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2004: ¥10,800,000 (Direct Cost: ¥10,800,000)
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| Keywords | FGFR3 / PTHrP / cartilage / ultrastructure / genetargeted mice / 軟骨細胞 / 遺伝子変異 / VEGF / 致死型軟骨無形成症 / 軟骨内骨化 / アポトーシス |
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| Research Abstract |
We conducted the broad analyses on the biological function of fibroblast growth factor receptor type III (FGFR3) and parathyroid hormone-related peptide (PTHrP), by employing gene targeted mice, cells transgenes with mutated PTH/PTHrP receptors and bone metastatic mice with PTHrP-overexpressing tumors. In 2004, we have generated FGFR3^<-/->/PTHrP^<-/-> mice, and examined the skeletal deformities on bone and cartilage. As a results, PTHrP dominantly affected on the chondrocyte proliferation, rather than FGFR3. However, FGFR3 could influence the apoptosis and VEGF expression in chondrocytes after their entry to hypertrophic phenotype. In 2005, we have reported that PTHrP stimulated osteoblastic proliferation and survival in an autocrine/paracrine manner. Also, we provided the strong possibility that proteins of mutated PTH/PTHrP receptors, inducing Jansen type and Blomstrand type chondrodysplasia, would be accumulated in endoplasmic reticulum, and subsequent be leaked into the cytoplasmic region. Therefore, the mutant receptors would not be normally targeted to the cell membranes. In addition, we have morphologically examined the metastastic lesion by PTHrP-overexpressing tumors. Thus, we assessed the skeletal pathological features caused by the mutations and abnormal expression of FGFR3 and/or PTHrP genes.
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