Change and Mechanism of Osteoclast/Osteoblast Coupling by Parathyroid Hormone
| Project/Area Number |
17K16168
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Endocrinology
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| Research Institution | Osaka City University |
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Principal Investigator |
Nagata Yuki 大阪市立大学, 大学院医学研究科, 病院講師 (20779483)
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 副甲状腺ホルモン / 破骨細胞 / 骨芽細胞 / カップリング因子 / 破骨細胞/骨芽細胞カップリング / 原発性副甲状腺機能亢進症 / 内分泌学 / 骨代謝 |
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| Outline of Final Research Achievements |
Parathyroid hormone (PTH) facilitates bone turnover. We studied the mechanisms responsible for the changes of EphrinB2/EphB4, which is bidirectional osteoclast (OCL)/osteoblast (OB) coupling factor. In mice treated with PTH, EphrinB2 on OCL and EphB4 on OB were increased in bone, compared to control mice. Mice treated with RANKL also increased EphrinB2, whereas mice treated with anti-RANKL antibody attenuated EphrinB2 in bone, compared to control mice. PTH did not change EphirinB2 on OCL; however, OCL/OB co-culture with PTH showed OCL formation and EphrinB2 were increased, whereas these effects were reversed by anti-mouse RANKL antibody. On the other hand, OB treated with EphrinB2-Fc increased RANKL and PTH had an additive effect, as well as ALP and Alizarin Red staining was increased. These results indicate that PTH augments EphrinB2 derived from OCL via increased RANKL in OB. In addition, EphrinB2 on OCL promotes OB differentiation and mineralization coordinately with PTH.
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| Academic Significance and Societal Importance of the Research Achievements |
PTH 間歇的投与は骨芽細胞による骨形成を促進し、骨密度・骨質を増加させる唯一の骨形成促進薬であり、それ以外の骨粗鬆症治療薬は、破骨細胞による骨吸収を抑制し、骨密度を増加させる骨吸収阻害薬が主流である。本研究により、PTHによって、骨組織における破骨細胞/骨芽細胞カップリング因子ephrinB2/EphB4の骨代謝回転における役割と、RANKLを介したの発現調節機構の存在が証明された。この機構が明らかになったことで、骨形成を促進させる新たなる骨粗鬆症の治療法につながる可能性があり、本研究はトランスレーショナルリサーチとして、非常に重要と考えられる。
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Report
(3 results)
Research Products
(7 results)
