Investigation of Novel isoform-specific signal transcution mechanisms of JNKs
| Project/Area Number |
17K11646
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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 |
Functional basic dentistry
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| Research Institution | Kagoshima University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
大西 智和 鹿児島大学, 医歯学域歯学系, 准教授 (30244247)
楠山 譲二 鹿児島大学, 医歯学総合研究科, 客員研究員 (70596105)
柿元 協子 鹿児島大学, 医歯学総合研究科, 客員研究員 (40274849)
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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: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 細胞分化 / 骨代謝 / 骨芽細胞 / 脂肪細胞 / 細胞内シグナル伝達 / 転写因子 / 骨形成タンパク質 / JNK / ホスファターゼ / キナーゼ / シグナル伝達 / アイソフォーム / 遺伝子発現 / 免疫応答 / 糖代謝 |
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| Outline of Final Research Achievements |
JNK is known as a multifunctional kinase controling various biological functions. There are 3 isoforms (JNK1/2/3) of JNK. However, exact functional differences among these isoforms have not been fully elucidated. We have previously identified isoform-specific regulatory functions of JNK in osteoblast differentiation. Here, we have newly revealed 1) JNK2 specifically play essential roles in the early differentiation process of adipocyte diffrentiation, 2) Osteopontin-dominant type of osteoblast differentiation is induced by JNK inhibition via a transcriptional regulator, Id4, and 3) BMP9 negatively inhibits osteopontin-dominant differentiation of osteoblasts via inhibiting Id4.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究によって、JNK活性がアイソフォーム特異的に、多分化能を持つ間葉系幹細胞から脂肪・骨細胞分化への制御に重要な働きをすること、また骨形成因子であるBMP9がそのプロセスに影響を与えることを明らかにした。本研究の成果は、超高齢化社会のQOL維持のために必須となってくる骨再生療法のよりよい臨床応用法の開発に繋がる重要な所見と考えられる。また、将来的には、JNKが発症に関与する炎症性疾患、糖尿病、がん、心血管障害などの疾患のより効率的な予防・治療法の開発に繋がることも期待される。
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Report
(4 results)
Research Products
(22 results)
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[Journal Article] JNK inactivation suppresses osteogenic differentiation, but robustly induces osteopontin expression in osteoblasts through the induction of inhibitor of DNA binding 4 (Id4).2019
Author(s)
Kusuyama J, Amir MS, Albertson BG, Bandow K, Ohnishi T, Nakamura T, Noguchi K, Shima K, Semba I, Matsuguchi T.
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Journal Title
FASEB J.
Volume: -
Issue: 6
Pages: 7331-7347
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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