| Project/Area Number |
09671868
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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 |
Morphological basic dentistry
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| Research Institution | Showa University |
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Principal Investigator |
KATAOKA Hiroko Showa University, School of Dentistry, Assistant, 歯学部, 助手 (60286846)
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| Co-Investigator(Kenkyū-buntansha) |
AIDA Tadateru Showa University, School of Dentistry, Assistant, 歯学部, 助手 (10307051)
YAMAGUCHI Akira Showa University, School of Dentistry, Associate Professor, 歯学部, 助教授 (00142430)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1997: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | Hedgehog / Sonic / Indian / osteoblast / bone formation / Bone morphogenetic protein / 培養細胞 / 分化 / マウス |
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| Research Abstract |
Hedgehogs play important roles during morphogenesis of various organs and tissues. Sonic hedgehog (Shh) knock our mice demonstrated that complete lack of vertebrae and autopods. In addition, Indian hedgehog (Ihh) is expressed in cartilage, and regulates cartilage differentiation. Although these results suggest that hedgehogs play important roles in osteoblast differentiation, the roles of hedgehogs in osteoblast differentiation have been fully investigated. In the present study, we conducted several experiments to investigate the roles of hedgehogs in osteoblast differentiation, and obtained the following results.
1. Using mouse fracture model, we investigated the expression patterns of various mRNAs. The expression of Shh mRNA was induced at 12-48 hours after fracture, and Ihh mRNA expression was induced after 72 hours of the fracture. The expression of mRNAs for Ptc and Gli, which is responding genes to Shh, increased after 12 hours of fracture.
2. Culture supernatants obtained from chicken embryonic fibroblasts (CEF) stimulated the expression levels of mRNAs for Ftc, Gli, and osteocalcin and the level of ALP activity in both C3H1OT1/2 and MC3T3-E1 cells. ALP activity induced by these culture supernatants was strongly inhibited by adding soluble BMP type IA receptor. These culture supernatants also induced expression of aggrecan mRNA in C3H1OTII2 cells but not in MC3T3-E1 cells. Recombinant SHH produced by E.coli failed to increase ALP in C3T1OT1/2 and MC3T3-E1 cells, but recombinant SHH synergistically stimulated ALP activity induced by BMP-2 in these cells.
3. Transplantation of CEF overexpressing Shh or Ihh into muscle in athymic mice induced formation of ectopic bones. Recombinant SHH synergistically induced ectopic bone formation induced by BMP-2 in mice muscle.
These results suggested that SHH and IHH might be involved in stimulation of bone formation during fracture repair in association with BMP-2.
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