Biological function of osteoporotic drugs on bone-specific blood vessels and perivascular cells

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K21006
• 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: Hokkaido University
• Principal Investigator: Maruoka Haruhi 北海道大学, 歯学研究院, 助教 (40962577)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: 血管連関 / ビスホスホネート / 活性型ビタミンD / 骨特異的血管 / 血管周囲細胞

Outline of Final Research Achievements

In the ALN administrated mice, the diameter and area of bone-specific blood vessels were decreased, and vascular endothelial cells formed numerous reticulum and microtubules toward the vascular lumen. It suggests that ALN causes microstructural changes in the vascular wall. The upregulation of endomucin, its transcription factors, and angiogenesis inhibitory factors, which are involved in maintaining the three-dimensional luminal morphology of the vascular wall, in bone tissue from ALN- administrated mice. It indicates that, while abnormal vascular microstructure and angiogenesis are suppressed, a repair mechanism may be at work to correct these abnormalities.
In addition, ALP-positive/PHOSPHO1-positive osteoblasts were markedly decreased in ALN-administrated mice, suggesting that ALN may also affect bone-specific blood vessels and osteoblasts.

Free Research Field

組織学、骨代謝学、微細構造学

Academic Significance and Societal Importance of the Research Achievements

現在用いられているPTHやビスホスホネート、活性型ビタミンD3製剤などの骨粗鬆症治療薬は、破骨細胞などの骨の細胞群への作用ばかりが注目されてきた。本研究では、骨粗鬆症治療薬の血管や血管周囲細胞に対する作用ならびに、薬剤が作用した血管・血管周囲細胞による骨芽細胞系細胞への影響を明らかにし、骨血管連関および骨代謝調節機構のメカニズムに焦点をあてることにより、骨粗鬆症治療薬の新規作用解明に取り組んでおり、高い学術的独創性と創造性に富んでいると思われる。ゆえに本研究開発により、骨粗鬆症治療薬の新規開発が進み、超高齢化社会となった現在において、健康寿命の延伸に寄与できると考えられる。