Project/Area Number |
17591965
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Pathobiological dentistry/Dental radiology
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Research Institution | Nagasaki University |
Principal Investigator |
SUMI Tadateru Nagasaki University, Graduate School of Biomedical Sciences, Instructor, 大学院医歯薬学総合研究科, 助手 (80284701)
|
Co-Investigator(Kenkyū-buntansha) |
SUMI Misa Nagasaki University, Graduate School of Biomedical Sciences, Associate Professor, 大学院医歯薬学総合研究科, 助教授 (90284702)
TASHIRO Shigeki Nagasaki University, Graduate School of Biomedical Sciences, Instructor, 大学院医歯薬学総合研究科, 助手 (20300882)
HOTOKEZAKA Yuka Nagasaki University, Hospital of Medicine and Dentistry, Assistant Professor, 医学部・歯学部附属病院, 講師 (10244089)
NAKAMURA Takashi Nagasaki University, Graduate School of Biomedical Sciences, Professor, 大学院医歯薬学総合研究科, 教授 (30172406)
|
Project Period (FY) |
2005 – 2006
|
Project Status |
Completed (Fiscal Year 2006)
|
Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2006: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2005: ¥2,000,000 (Direct Cost: ¥2,000,000)
|
Keywords | regenerative medicine / histology and cell biology / signaling passway / radiology / odontology |
Research Abstract |
Osteocasts are believed necessary for the repair of extraction socket. A cPLA_2, metabolite PGE2 has been repoted to be negative regulation of osteoclastic function. However, it is not still uncertain whether cPLA_2 per se is involved in the regulation of osteoclastic activity. In this study, we tested the possibility that cPLA_2 activity is necessary for osteoclastogenesis. Further, we investigated the role of cPLA_2 in the cell-fusion mechanism in multinucleated cell formation of osteoclasts and myocytes Changes in subcellular distributions of cPLA_2 and actin after initiation of multinucleated cell formation. Subcellular localizations of cPLA_2 and actin were analyzed by using a confocal laser scanning microscope. The cPLA_2 and actin were distributed throughout the cytoplasm of non-treated RAW264.7 cells. However, there proteins were predominantly distributed at the periphery of the RANKL-treated RAW264.7 cells. Effects of cPLA_2 inhibition in multinucleated cell formation. Next, we assessed the role of cPLA_2 in the multinucleated cell formation and in the regulation of bone resorption ability of RANKL-treated RAW264.7 cells by using the specific cPLA_2, inhibitors or the cPLA_2 siRNA. We found that the cPLA_2 inhibitors (AACOCF3 and MAFP) or cPLA_2 siRNA significantly inhibited multinucleated cell formation and in vitro bone resorption ability of RAW264.7 cells. cPLA_2 involvement in multinucleated myocyte formation of C2C12 cells. We found that multinucleated myocyte formation in C2C12 was also inhibited by the cPLA_2 inhibitors or RNA interference. Together, these results suggest that cPLA_2 may be deeply involved in osteoclastogenesis and myogenesis. A part of the above results was reported at the 47th Congress on Japanese Society for Oral and Maxillofacial Radiology (May, 2006, Tokyo).
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