Pyrophosphate regulatory mechanism in bone mineralization
| Project/Area Number |
20K08256
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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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| Review Section |
Basic Section 52050:Embryonic medicine and pediatrics-related
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| Research Institution | Osaka University |
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Principal Investigator |
Kubota Takuo 大阪大学, 大学院医学系研究科, 准教授 (40629135)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 骨代謝 / リン酸 / 間葉系幹細胞 / 非古典的Wntシグナル / 小児内分泌学 / 骨代謝学 / 骨石灰化 / 骨芽細胞分化 / Wntシグナル / ピロリン酸 / リン |
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| Outline of Research at the Start |
骨格の石灰化にはカルシウム、無機リン（Pi）、石灰化阻害物質のピロリン酸（PPi）が重要な役割を果たしているが、骨石灰化過程の調節機構は十分には明らかではない。骨石灰化に適切なPPi濃度、PPi/Pi比は明らかではなく、骨石灰化に関与する分子の全体像も解明されていない。さらに、骨石灰化の程度を反映するバイオマーカーや遺伝子発現プロファイルは存在しない。本研究では、骨石灰化に適切なPPi濃度、PPi/Pi比、骨石灰化関連新規物質、骨石灰化の程度を反映するバイオマーカーや遺伝子発現プロファイルを明らかにする。
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| Outline of Final Research Achievements |
Phosphate is an essential mineral for bone formation. However, the mechanism by which phosphate promotes osteogenic differentiation is not fully understood. We induced differentiation of human bone marrow-derived mesenchymal stem cells (MSCs) into osteoblasts using media containing β-glycerophosphate or inorganic phosphate which resulted in different phosphate concentrations. In this study, we found that phosphate upregulates the expression of WNT5b, WNT11, and phosphorylated c-Jun during early differentiation of MSCs into osteoblasts, activates the non-canonical Wnt signaling pathway, and promotes osteogenic differentiation.
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| Academic Significance and Societal Importance of the Research Achievements |
骨の正常な発達・恒常性維持は人間の健康にとって重要であり、骨形成を担う骨芽細胞分化のメカニズムを探ることは、骨形成の生理や代謝性骨疾患の病態の研究に不可欠である。我々は、本研究でリン酸によって誘導される骨芽細胞分化の初期段階における非古典的Wntシグナル伝達経路の活性化の関与について示した。これらの知見は、骨形成分化におけるリン酸と非古典的Wntシグナル伝達経路の関連について新たな視点を提供する。
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Report
(4 results)
Research Products
(24 results)
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[Journal Article] Genotype-phenotype analysis, and assessment of the importance of the zinc-binding site in PHEX in Japanese patients with X-linked hypophosphatemic rickets using 3D structure modeling2021
Author(s)
Ishihara Y, Ohata Y, Takeyari S, Kitaoka T, Fujiwara M, Nakano Y, Yamamoto K, Yamada C, Yamamoto K, Michigami T, Mabe H, Yamaguchi T, Matsui K, Tamada I, Namba N, Yamamoto A, Etoh J, Kawaguchi A, Kosugi R, Ozono K, Kubota T
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Journal Title
Bone
Volume: 153
Pages: 116135-116135
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Genotype-phenotype analysis, and assessment of the importance of the zinc-binding site in PHEX in Japanese patients with X-linked hypophosphatemic rickets using 3D structure modeling.2021
Author(s)
Ishihara Y, Ohata Y, Takeyari S, Kitaoka T, Fujiwara M, Nakano Y, Yamamoto K, Yamada C, Yamamoto K, Michigami T, Mabe H, Yamaguchi T, Matsui K, Tamada I, Namba N, Yamamoto A, Etoh J, Kawaguchi A, Kosugi R, Ozono K, Kubota T
Organizer
2021 Annual Meeting of the American Society for Bone and Mineral Research
Related Report
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[Presentation] Clinical, Biochemical and Genetic Study in Patients with Odontohypophosphatasia in Japan2020
Author(s)
Kubota T, Ohata Y, Ishihara Y, Fujiwara M, Takeyari S, Yamamoto K, Nakano Y, Kitaoka T, Nakayama H, Yamada C, Ishimi T, Okawa R, Nakano K, Akiyama T, Kakimoto H, Araki S, Sano S, Ogata T, Ozono K.
Organizer
ASBMR 2020 Annual Meeting
Related Report
Int'l Joint Research
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