Mechanosensor protein p130Cas in osteocytes is important for bone metabolism
Project/Area Number |
24592290
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Orthopaedic surgery
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Research Institution | Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology |
Principal Investigator |
MIYAZAKI TSUYOSHI 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究員 (50376480)
|
Co-Investigator(Kenkyū-buntansha) |
MIYAMOTO Yoshinaro 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究員 (10345217)
|
Project Period (FY) |
2012-04-01 – 2015-03-31
|
Project Status |
Completed (Fiscal Year 2014)
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Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
|
Keywords | メカニカルストレス / 骨細胞 / p130Cas |
Outline of Final Research Achievements |
The adaptor molecule p130Cas, which is phosphorylated at focal adhesions upon extracellular matrix engagement, is involved in various cellular processes including migration, survival, transformation, and invasion. To investigate the role of Cas in bone metabolism, we generated osteocyte-specific Cas conditional knockout (cKO) mice by mating Casflox/flox mice with Dmp1-Cre transgenic mice, in which the Cre recombinase gene was specifically expressed in osteocytes. The resulting Cas cKO mice exhibited a remarkable decrease in bone volume. Histomorphometric analysis of Cas cKO mice revealed a significant increase in the eroded surface/bone surface ratio, osteoclast surface, and osteoclast number. However, the bone formation parameters were equivalent to those in normal Casflox/flox littermates. Collectively, these findings suggest that the bone loss in Cas cKO mice was caused by increased bone-resorbing activity, rather than by decreased bone formation.
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Report
(4 results)
Research Products
(17 results)
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[Presentation] A novel murine model of myasthenia gravis with MuSK antibodies.2012
Author(s)
Mori, S., Kubo, S., Akiyoshi, T., Yamada, S., Miyazaki, T., Hotta, H., Desaki, J., Kishi, M., Konishi, T., Maruyama, N. and Shigemoto, K
Organizer
12th International conference on myasthenia gravis and related disorders
Place of Presentation
New York
Related Report
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[Presentation] Examination of the treatment of myasthenia gravis with anti-MuSK antibodies using an experimental autoimmune animal model. 12th International conference on myasthenia gravis and related disorders2012
Author(s)
Mori, S., Kubo, S., Akiyoshi, T., Yamada, S., Miyazaki, T., Hotta, H., Desaki, J., Kishi, M., Konishi, T., Maruyama, N. and Shigemoto, K.
Organizer
12th International conference on myasthenia gravis and related disorders
Place of Presentation
New York
Related Report
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[Presentation] Effectiveness of 3,4-diaminopyridine to symptomatic treatment of a MuSK antibody-induced mouse model of myasthenia gravis2012
Author(s)
Mori, S., Kubo, S., Akiyoshi, T., Yamada, S., Miyazaki, T., Kishi, M. and Shigemoto, K.
Organizer
第35回日本神経科学大会
Place of Presentation
名古屋
Related Report
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[Presentation] Muscle fiber type specific pathology in aging mouse.2012
Author(s)
Fukunaga, T., Kubo, S., Mori, S., Miyazaki, T., Higami, Y. and Shigemoto, K.
Organizer
第35回日本分子生物学会年会
Place of Presentation
福岡
Related Report