| Project/Area Number |
15K09540
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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 |
Collagenous pathology/Allergology
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| Research Institution | Kawasaki Medical School |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
守田 吉孝 川崎医科大学, 医学部, 教授 (50346441)
佐藤 稔 川崎医科大学, 医学部, 准教授 (70449891)
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| Research Collaborator |
UEKI YASUYOSHI 米国ミズーリ大学, カンザスシティ校, Associate Professor
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | SH3BP2 / Tankyrase / 破骨細胞 / 骨代謝 / 骨芽細胞 / NFATc1 / 全身性エリテマトーデス / マクロファージ / 骨粗鬆症 / 自己免疫疾患 |
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| Outline of Final Research Achievements |
Tankyrase, a poly (ADP-ribose) polymerase, is reported to degrade an adaptor protein SH3BP2 (SH3 domain-binding protein 2). We have previously shown that SH3BP2 gain-of-function mutation enhances RANKL-induced osteoclastogenesis in murine bone marrow-derived macrophages. Although the interaction between tankyrase and SH3BP2 has been reported, it is not clear whether and how the inhibition of tankyrase affects bone cells and bone mass. Here, we have demonstrated that tankyrase inhibitors enhanced RANKL-induced osteoclast formation and function in murine BMMs through the accumulation of SH3BP2, subsequent nuclear translocation of NFATc1. Tankyrase inhibitors also enhanced osteoblast differentiation and maturation, represented by increased expression of osteoblast-associated genes. Most importantly, pharmacological inhibition of tankyrase in mice significantly decreased tibia and lumbar vertebrae bone volumes in association with increased numbers of osteoclasts.
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