| Project/Area Number |
18592208
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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 |
Surgical dentistry
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| Research Institution | Matsumoto Dental University |
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Principal Investigator |
TAKAHASHI Masahiro Matsumoto Dental University, DEPARTMENT OF ORAL MAXILLOFACIAL SURGERY, ASSISTANT PROFESSOR (90340059)
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| Co-Investigator(Kenkyū-buntansha) |
UEMATSU Takashi MATSUMOTO DENTAL UNIVERSITY, DEPARTMENT OF ORAL MAXILLOFACIAL SURGERY, ASSOCIATE PROFESSOR (40203476)
UDAGAWA Nobuyuki MATSUMOTO DENTAL UNIVERSITY, DEPARTMENT OF BIOCHEMISTRY, PROFESSOR (70245801)
YAMASHITA Teruhito MATSUMOTO DENTAL UNIVERSITY, DEPARTMENT OF BIOCHEMISTRY, ASSISTANT PROFESSOR (90302893)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,690,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | DOCETAXEL / BONE RESORPTION / OSTEOBLAST / OSTEOCLAST / MICROTUBULES |
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| Research Abstract |
Bone-resorbing osteoclasts are differentiated from the monocyte-macrophage lineage cells in response to receptor activator of nuclear factor KB (RANKL) expressed by osteoblasts. Docetaxel (Taxotere^<R>) is widely used for the treatment for many kinds of cancers including breast, ovarian and oral cancers. Using mouse culture systems, we explored the effects of docetaxel on osteoclastic bone resorption. Osteoclasts were formed within 6 days in cocultures of mouse osteoblasts and bone marrow cells in the presence of 1, 25-dihydroxyvitamin D_3 [1, 25(OH)_2D_3] together with prostaglandin B_2 (PGE_2). When cocultures were treated with docetaxel for the entire culture period or for the first 3 days, docetaxel dose-dependently inhibited osteoclast formation induced by 1, 25(OH)_2D_3 plus PGE_2 with the complete inhibition at 10^<-8>M. However, docetaxel even at 10^<-6> added to the coculture for the fmal 3 days slightly inhibited the osteoclast formation. Osteoprotegerin, a decoy receptor of RANKL, added to the coculture for the entire culture period or the fmal 3 days completely inhibited osteoclast formation. Expression of RANKL induced by 1, 25(OH)_2D_3 plus PGE_2 in osteoblasts was not affected by docetaxel even at 10^<-6>M. Docetaxel at 10^<-8>M inhibited proliferation of osteoblasts and bone marrow cells. In contrast, the pit-forming activity of osteoclasts placed on dentine slices was not inhibited by docetaxel even at 10^<-7>M but inhibited at 10^<-6>M or more. These results suggest that docetaxel inhibits bone resorption in two different processes: inhibition of osteoclast formation at 10^<-8>M, and function of mature osteoclasts at 10^<-6>M or more.
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