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Functional Study of Pyk2-related signaling for developing novel bone anabolic drugs [an abstract of entire text]
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| Title: | Functional Study of Pyk2-related signaling for developing novel bone anabolic drugs [an abstract of entire text] |
| Other Titles: | 骨形成促進薬の新規開発に向けたPyk2シグナルの機能解析 [全文の要約] |
| Authors: | 劉, 雲青 Browse this author |
| Issue Date: | 24-Mar-2022 |
| Publisher: | Hokkaido University |
| Abstract: | Cumulative studies indicated that the proline-rich tyrosine kinase 2 (Pyk2) is anegative regulator of bone formation but the molecular mechanisms whereby Pyk2functions in osteogenic differentiation are not fully understood. In the current study, weprovided insight into the role of Pyk2 inhibition in osteoblastic differentiation using aPyk2-targeted inhibitor; PF-4618433 (PF-46). Treatment of osteoblastic differentiationfrom a bone marrow stromal cell line of ST2 cells with PF-46 significantly stimulatedALP activity and mineralization. In contrast, the concomitant inhibition of both FAKkinase and Pyk2 kinase by a dual FAK/Pyk2-inhibitor; PF-431396 (PF-43) reducedosteogenic function. Real-time PCR analyses showed that osteogenic markers such asALP, Runx2, Col1a1, Opg and Ocn were upregulated by PF-46, suggesting that Pyk2inhibition accelerate the osteoblastic differentiation in ST2 cells. In addition, PF-46markedly increased the canonical Wnt/β-catenin signaling related genes expression,such as Wnt1, β-catenin, Gsk-3β and Lef, indicating Pyk2 inhibition is involved inWnt-mediated osteogenesis. PF-46 also promoted stabilization of β-catenin in thecytoplasm and translocation into nuclear in ST2 cells. Our study suggest that Pyk2inhibition promotes osteoblast differentiation as a regulator of Wnt1-mediated boneformation, providing new insights into the treatment of osteoporosis. |
| Description: | この博士論文全文の閲覧方法については、以下のサイトをご参照ください。 |
| Description URI: | https://www.lib.hokudai.ac.jp/dissertations/copy-guides/ |
| Conffering University: | 北海道大学 |
| Degree Report Number: | 甲第15013号 |
| Degree Level: | 博士 |
| Degree Discipline: | 歯学 |
| Examination Committee Members: | (主査) 教授 飯村 忠浩, 教授 田村 正人, 教授 網塚 憲生 |
| Degree Affiliation: | 歯学院（口腔医学専攻） |
| Type: | theses (doctoral - abstract of entire text) |
| URI: | http://hdl.handle.net/2115/85929 |
| Appears in Collections: | 課程博士 (Doctorate by way of Advanced Course) > 歯学院(Graduate School of Dental Medicine)
学位論文 (Theses) > 博士 （歯学）
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