| 研究課題/領域番号 |
23K09116
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| 研究種目 |
基盤研究(C)
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| 配分区分 | 基金 |
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| 応募区分 | 一般 |
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| 審査区分 |
小区分57010:常態系口腔科学関連
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| 研究機関 | 北海道大学 |
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研究代表者 |
李 智媛 北海道大学, 歯学研究院, 助教 (70711274)
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| 研究分担者 |
飯村 忠浩 北海道大学, 歯学研究院, 教授 (20282775)
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| 研究期間 (年度) |
2023-04-01 – 2026-03-31
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| 研究課題ステータス |
交付 (2023年度)
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| 配分額 *注記 |
4,680千円 (直接経費: 3,600千円、間接経費: 1,080千円)
2025年度: 1,820千円 (直接経費: 1,400千円、間接経費: 420千円)
2024年度: 1,430千円 (直接経費: 1,100千円、間接経費: 330千円)
2023年度: 1,430千円 (直接経費: 1,100千円、間接経費: 330千円)
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| キーワード | Pyk2 / osteoclasts / microglia / ontogeny / osteoporosis / Alzheimer's disease / osteoclast / PTK2B |
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| 研究開始時の研究の概要 |
To find functional roles of Pyk2 that are associated between osteoporosis and AD, we will 1) elucidate physiological mechanism of Pyk2 in osteoclast and microglia, and 2) dissociate role of Pyk2 inhibition in pathophysiology of osteoporosis and AD using mouse disease model.
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| 研究実績の概要 |
Our first-year plan is as follows: Elucidating the molecular mechanism of Pyk2 on the ontogeny of osteoclasts and microglia in vitro, using Pyk2 inhibitor. Following the plan, we conducted molecular biology investigations into the effects of utilizing a target inhibitor of Pyk2, a convergence gene we discovered, on osteoclasts and microglia. We demonstrated that inhibiting Pyk2 in microglia enhances phagolysosomal activities against Aβ oligomers both in vitro. In vivo, the administration of the Pyk2 inhibitor led to an increased migration of microglia toward deposits in the brains of Iba-1 EGFP transgenic mice, accompanied by morphological activation, suggesting a heightened affinity for Aβ. Furthermore, we confirmed that Pyk2 inhibitor inhibited the osteoclast differentiation. In vitro, Pyk2 inhibition significantly impedes osteoclast differentiation and bone resorption. In a co-culture system comprising osteoblasts and osteoclasts, Pyk2 inhibitor effectively suppressed osteoclast differentiation, accompanied by a substantial increase in the transcriptional expression of Tnfrsf11b and Csf1 in osteoblasts.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
My research is progressing as planed in proposal.
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| 今後の研究の推進方策 |
By employing a 3rd generation double tg (App/Psen1) mouse model for AD, and harnessing cutting-edge analytical tools like FTIR imaging and spatial transcriptomics, we aim to evaluate the impact of Pyk2 inhibition on Aβ deposition.
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