| Project/Area Number |
21890071
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
NOUTOMI Takuya Tokyo Medical and Dental University, 歯と骨のGCOE拠点, GCOE拠点形成特任教員 (70542249)
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| Project Period (FY) |
2009 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2010: ¥1,235,000 (Direct Cost: ¥950,000、Indirect Cost: ¥285,000)
Fiscal Year 2009: ¥1,365,000 (Direct Cost: ¥1,050,000、Indirect Cost: ¥315,000)
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| Keywords | 骨 / 破骨細胞 / イオンチャネル / HCN |
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| Research Abstract |
Our study focused on one of ion channels, pacemaker channel (HCN) in bone. HCN1 is localized around ruffled border area where osteoclast secretes acid. To elucidate the role of HCNs, HCN1 deficient mice were hired. The role of HCN3 in osteoblasts was investigated.
1 : In HCN1-deficient mice, trabecular bone mass and the structural parameter of Trabecular Number were significantly lower, whereas Trabecular Separation was significantly higher, in HCN1-KO than in wild type (WT). Histomorphometiric indices of bone formation (MAR and BFR/BS) and resorption (Oc.S/BS and Oc.N/BS) were increased.
2 : Patch clamp recordings showed that HCN1-deficiency decreased the activation rate of the hyperpolarization-activated current although the amplitude was same as WT, probably because other HCN subtypes remained intact.
3 : Overexpression of HCN3 by transfecting the gene enhanced proliferation of WT-osteoblasts as measured by total cell number.
4 : Osteoclastic Ih was significantly reduced by knockdown of HCN4, suggesteing that osteoclastic Ih could be generated from HCN1 and HCN4.
The high bone turnover in HCN1-KO was likely to be based on cellular dysfunctions. HCN1 could modulate acid secretion and differentiation in osteoclasts. In addition, lack of HCN1 upregulated expression of HCN3 in osteoblasts. HCN3 may contribute to osteoblastic bone formation.
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