Elucidation of lymph node metastasis inhibition mechanism of oral cancer targeting sphingomyelin synthetase
| Project/Area Number |
16K11710
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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 |
Surgical dentistry
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| Research Institution | Kanazawa Medical University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | スフィンゴミエリン合成酵素 / スフィンゴミエリン / 骨粗しょう症 / 骨芽細胞 / BMP2 / 骨芽細胞分化 / 骨粗鬆症 / 骨代謝 / 扁平上皮癌 / リンパ節転移 / SMS1 / SMS2 / sphingomyelin / osteoblast / 口腔癌 / セラミド |
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| Outline of Final Research Achievements |
We analyzed the phenotype of a conditional knockout mouse, which was generated by mating a Sp7 promoter-driven Cre-expressing mouse with an SMS1-floxed SMS2-deficient mouse (Sp7-Cre;SMS1f/f;SMS2-/- mouse). When we compared control mice, we found that although cartilage formation is normal, Sp7-Cre;SMS1f/f;SMS2-/-mice showed reduced trabecular and cortical bone mass, had lower bone mineral density, and had a slower mineral apposition rate. We have used a tamoxifen-inducible knockout system in vitro to show that SMS1 plays an important role in osteoblast differentiation and mineralization. We cultured osteoblasts derived from SMS1-CreERT2;SMS2-/- mice. We observed impaired differentiation of these cells in response to Smad1/5/8 and p38 that were induced by BMP2. SMS1 acts as an endogenous signaling component necessary for bone formation.
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| Academic Significance and Societal Importance of the Research Achievements |
スフィンゴミエリンは細胞膜の重要な構成成分で、脂質マイクロドメインと呼ばれるコレステロールに富む領域を形成する。脂質マイクロドメインには増殖因子受容体や細胞内シグナル伝達分子などが局在し様々な細胞生理活性に関与している。SMの合成を触媒するスフィンゴミエリン合成酵素にはSMS1とSMS2があるが、その生理的な機能については十分に解明されていない。本研究においてSMS1が骨芽細胞の分化に重要な役割を担い、SMS1が欠損していると、ヒトにおける骨粗しょう症と同様の症状を示すことを明らかにした。これはSMS1を標的とした骨粗しょう症に対する新たな治療戦略を提案できる可能性が示された。
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Report
(4 results)
Research Products
(3 results)
