Regulation of pathological bone destruction targeting membrane molecules expressed in pathologically activated osteoclasts

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K24098
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0907:Oral science and related fields
• Research Institution: Kyushu University
• Principal Investigator: Kyumoto-Nakamura Yukari 九州大学, 歯学研究院, 助教 (40729026)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: 破骨細胞 / 骨吸収 / IL-1β

Outline of Final Research Achievements

We have previously showed that osteoclasts formed in the presence of IL-1β enhanced bone resorption and induced the expression of cell surface protein different from normal osteoclasts. IL-1β stimulation induced expression of Transferrin receptor 1 (TfR1) in osteoclasts and enhanced iron uptake into cells through TfR1. However, known pathways involved in regulation of TfR1 expression and enhancement of bone resorption was not significantly affect by IL-1β stimulation in osteoclasts. Therefore, IL-1β enhances bone resorption by increasing intracellular iron through up-regulation of TfR1 expression, but the mechanism is not yet clear.

Free Research Field

分子口腔解剖学

Academic Significance and Societal Importance of the Research Achievements

本研究の遂行により、病的骨破壊を制御する候補分子としてTfR1を示すことができた。正常な破骨細胞にも発現しているTfR1がIL-1β刺激によりさらに発現が上昇し、骨吸収が亢進するという申請者が得た知見はこれまでに報告はなく、まだ不明な点が多い破骨細胞における病的機能亢進のメカニズム解明につながる可能性を秘めた重要な結果である。また本研究結果は、通常の生理的機能には影響を与えずに病的骨吸収のみを標的としたより副作用の少ない安全な新しい骨破壊疾患治療薬の開発への足掛かりになることが期待される。