The function of an adaptor protein SH3BP2 in inflammatory bone destruction and autoimmune diseases
| 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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Report
(4 results)
Research Products
(26 results)
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[Presentation] Tankyrase regulates bone mass and osteoclastogenesis2017
Author(s)
Shunichi Fujita, Tomoyuki Mukai, Takafumi Mito, Shoko Kodama, Akiko Nagasu, Hiroyasu Hirano, Yoshitaka Morita
Organizer
The 61th Annual General Assembly and Scientific Meeting of the Japan College of Rheumatology
Place of Presentation
福岡国際会議場、福岡市、福岡県
Year and Date
2017-04-21
Related Report
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[Presentation] SH3BP2 Gain-of-Function Mutation Ameliorates Lupus in B6.MRL-Faslpr Mice2017
Author(s)
Akiko Nagasu, Tomoyuki Mukai, Masanori Iseki, Hajime Nagasu, Shunichi Fujita, Takafumi Mito, Shoko Kodama, Yumi Sasae, Naoki Kashihara, Katsuhiko Ishihara, Yasuyoshi Ueki and Yoshitaka Morita
Organizer
The 2017 ACR/ARHP Annual Meeting
Related Report
Int'l Joint Research
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