Elucidation of regulatory mechanisms of skeletal via Smad4
| Project/Area Number |
17K11026
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Saitama Medical University |
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Principal Investigator |
Tsukamoto Sho 埼玉医科大学, 医学部, 助教 (20707658)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 骨形成 / 骨系統疾患 / 骨粗鬆症 / シグナル伝達 / 骨代謝 / 骨・軟骨代謝学 / 内軟骨性骨化 / 骨、軟骨代謝学 |
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| Outline of Final Research Achievements |
Members of the transforming growth factor-β (TGF-β) family regulate skeletal formation through activating Smad transcription factors. Smad4 is a critical coactivator essential for the Smad-dependent intracellular signaling. We established Smad4 conditional knockout (Smad4 cKO) mice under the control of tamoxifen. The Smad4 cKO mice showed an increase in bone mass in trabecular bone. They also showed an increase in β-catenin positive osteoblasts in spongiosa. The analysis of the Wnt signaling related genes revealed that expression of Wnt7b was increased in Smad4 cKO mice. These results suggest that the inhibition of Smad4-dependent signaling enhances bone formation through increased expression of Wnt7b.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究から、出生後におけるSmad4を介したシグナルは、骨形成を抑制している可能性を見出した。さらに、TGF-βファミリーと骨形成を強力に亢進するWntシグナルの新たなクロストークの発見は、骨粗鬆症をはじめとした骨代謝関連の疾患の新たな治療標的となる可能性がある。
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Report
(4 results)
Research Products
(31 results)
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[Presentation] A role of dimer formation of ALK2, a BMP typeI receptor in the activation of intracellular signaling2019
Author(s)
Katagiri T, Tsuji S, Tsukamoto S, Kuratani M, Ohte S, Sekine N, Kumagai K, Osawa K, Takaishi K, Nakamura K, Kawaguchi Y, Hasegawa J
Organizer
Gordon Research Conference on Cartilage
Related Report
Int'l Joint Research
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[Presentation] Development of blocking monoclonal antibodies against ALK2, which is a type I receptor for BMPs2017
Author(s)
Katagiri T, Tsuji S, Tsukamoto S, Ohte S, Kumagai K, Osawa K, Takaishi K, Nakamura K, Kawaguchi Y, Hasegawa J
Organizer
2017 FASEB Science Research Conferences on The TGF-β Superfamily
Related Report
Int'l Joint Research
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[Presentation] Development of blocking monoclonal antibodies against ALK2, which is a type I receptor for BMPs2017
Author(s)
Katagiri T, Tsuji S, Tsukamoto S, Ohte S, Kumagai K, Osawa K, Takaishi K, Nakamura K, Kawaguchi Y, Hasegawa J
Organizer
2017 ASBMR Annual Meeting
Related Report
Int'l Joint Research
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