Analysis on the physiological role of osteocytic small extracellular vesicles in the bone remodeling

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K22676
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 56:Surgery related to the biological and sensory functions and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: Ikebuchi Yuki 東京大学, 医学部附属病院, 助教 (20645725)
• Project Period (FY): 2019-06-28 – 2021-03-31
• Keywords: 骨細胞 / 細胞外膜小胞 / アポトーシス小体 / 細胞老化

Outline of Final Research Achievements

IDG-SW3 and MLO-Y4 cells, which are osteocyte-like cell lines, were cultured in several conditions to examine the profile of RANKL expression. As a result, typical features of the cellular senescence were observed in IDG-SW3 cells under normal concentration of oxygen, at 20%. Furthermore, RANKL secretion to culturing media was increased in the senescence cells, and most of RANKL molecules were detected in the fraction of small extracellular vesicles. These results indicated that cellular senescence in osteocytes, induced by oxidative stress, may be involved in the osteoclasts formation via RANKL-containing small extracellular vesicles. On the other hand, apoptosis in MLO-Y4 cells resulted in ATP release and it induced RANKL expression in surrounding MLO-Y4 cells. Further analysis will be needed to reveal these multi-factors mechanism, therefore several gene-manipulated mice was established.

Free Research Field

骨代謝

Academic Significance and Societal Importance of the Research Achievements

骨代謝回転の起点となる破骨細胞形成が、時間的・空間的にどの様に制御されているのかは未解明な点が多い。本研究から、高酸素濃度への暴露による細胞老化誘導と、アポトーシスに伴うATP放出という2つの異なるメカニズムで、破骨細胞形成の中心因子であるRANKLの発現制御が行われる可能性が見出された。これは、骨代謝回転の全体像を理解する上で重要な知見を得られたと考えている。さらに、これら骨細胞からのRANKL提示は細胞外膜小胞に搭載されて起こりうることも示唆され、将来的に、これらを標的とした抗体分子の投与によって骨代謝回転の制御が可能になることを期待している。