| Project/Area Number |
05557080
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| Research Category |
Grant-in-Aid for Developmental Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Functional basic dentistry
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| Research Institution | TOKYO MEDICAL AND DENTAL UNIVERSITY |
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Principal Investigator |
KASUGAI Shohei TOKYO MED.& DENT.UNIV.FAC.OF DENT.ASSOCIATE PROFESSOR, 歯学部, 助教授 (70161049)
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| Co-Investigator(Kenkyū-buntansha) |
MATAKI Shiro NAGASAKI UNIV.FAC.OF DENT.ASSOCIATE PROFESSOR, 歯学部, 助教授 (80157221)
SUZUKI Shoichi TOKYO MED.& DENT.UNIV.FAC.OF DENT.ASSISTANT, 歯学部, 助手 (90187732)
SHIBATA Shunichi TOKYO MED.& DENT.UNIV.FAC.OF DENT.ASSISTANT, 歯学部, 助手 (80187400)
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 1994: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1993: ¥2,900,000 (Direct Cost: ¥2,900,000)
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| Keywords | BONE / OSTEOBALST / PROSTAGLANDIN / RECEPTOR / SIGNAL TRANSDUCTION / 骨芽細胞 / 破骨細胞 / 骨髄 / プロスタグランディン |
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| Research Abstract |
Administration of prostaglandin E_2 (PGE_2) has anabolic effects in bone, we examined the effects of PGE_2 on bone-like mineralized tissue formation in rat bone marrow stromal cell culture. Addition of PGE_2 at early stage of culture increased the amount of mineralized tissue whereas addition of PGE_2 at later stage, just before mineralization, inhibited mineralized tissue formation, indicating that effects of PGE_2 is depending on the stage of osteoblastic differentiation. Then, we tried to find the signal transduction pathway of the anabolic effect of PGE_2 at the early stage of this culture system, and our experiment revealed the involvement of cAMP-dependent signal transduction in this phenomenon. On the other hand, PGE_2 increases intracellular Ca, and stimulates or inhibits cAMP production through PGE receptor subtypes ; EP_1, EP_2 and EP_3, respectively. These receptor subtypes have been recently cloned. We investigated the expression of these receptor subtypes in bone tissue. RT-PCR revealed that EP_1, EP_2 and EP_3 were expressed in rat calvaria and that osteoblastic cells (MC3T3-E1) expressed EP_1 and EP_2. In situ hybridization analysis using cryosection of neonatal calvariae revealed that EP_2 was expressed by osteoblasts and cells not in contact with bone, probably including preosteoblasts. EP_2 expression was observed at an early stage in calvarial development, and also in rat bone marrow cell culture. It has been established that PGE_2 response accompanying cAMP production is one of the characteristics of osteoblasts. Our results indicate that this phenotype appears at an early stage of osteoblastic differentiation and bone development.
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