Elucidation of sex-specific signaling pathways in female-specific osteoblasts and their application to osteoporosis therapies.

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09659
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Matsumoto Dental University (2021); Kindai University (2019-2020)
• Principal Investigator: Ishida Masayoshi 松本歯科大学, 総合歯科医学研究所, 講師 (50643251)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 骨粗鬆症 / 骨芽細胞 / シグナル伝達因子

Outline of Final Research Achievements

PAI-1 is an inhibitor of plasminogen activator (PA), which is important for the fibrinolytic system and is known to be involved in the pathogenesis of various diseases other than hemostasis such as osteoporosis. We previously showed that PAI-1 is involved in the pathogenesis of diabetic osteoporosis only in female mice and suppresses osteoblast differentiation and function only in female-derived osteoblasts.
Therefore, we used comprehensive gene expression analysis to extract genes whose expression was increased by PAI-1 stimulation in female osteoblasts, and RanBP3L was extracted, and functional analysis of the RanBP3L gene showed that it suppressed osteoblast function and differentiation, suggesting that the RanBP3L gene is involved in the PAI-1-mediated differentiation of osteoblasts in females. This suggests that the RanBP3L gene is involved in the pathogenesis of diabetic osteoporosis.

Free Research Field

骨代謝

Academic Significance and Societal Importance of the Research Achievements

骨粗鬆症の病態形成において、明らかな性差が認められ、これまでは、多くの研究において、性ホルモンの作用機構という観点から、多くの研究が進められてきた。しかし、性ホルモン以外の性差を説明する機構については、ほとんど何もわかっていないのが現状である。本研究成果は性ホルモン関連以外の骨粗鬆症病態を説明する新規な因子を見出したところに学術的意義があり、骨粗鬆症の発症の機序を解明し、治療薬の開発につながる点において社会的意義がある。