Elucidation of the mechanisms of osteoclastgenesis by membrane vesicles secreted from mechanical stress loadeed osteocyte.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K11722
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Mie University
• Principal Investigator: Itoh Tomohiro 三重大学, 生物資源学研究科, 准教授 (30435854)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 骨細胞 / 膜小胞 / メカニカルストレス / 破骨細胞 / 分化

Outline of Final Research Achievements

It was found that membrane vesicles secreted from osteocytes subjected to mechanical stress have the ability to induce osteoclast differentiation. The mechanism of this induction may involve proteins that are internalized by the mechanical stimuli. The N-glycans of the putative osteoclast differentiation-inducing protein contained in the membrane vesicles have been reported to be involved in the induction of osteoclast differentiation. And the increased amount of α-2, 6-sialic acid-modified N-glycans in the lectin chip array analysis in this research strongly support the involvement of the putative protein.
Fluorescence microscopy and single cell analysis revealed that membrane vesicles secreted from osteocytes were mostly taken up by progenitor osteoclasts and some of them were transformed into osteoclasts.

Free Research Field

健康科学

Academic Significance and Societal Importance of the Research Achievements

運動など骨に荷重負荷を与えるとその荷重に適応する骨の強度を上げるために既存の骨をまず壊す工程が始まる。本研究では、この骨溶解の機構に荷重負荷のセンサー細胞である骨細胞が分泌する膜小胞が関与していることを明らかにすることができた。さらに、この骨細胞からの膜小胞だけでは分化誘導は調節されておらず、この膜小胞を受容する前駆破骨細胞の表現系（型）も重要であることが明らかとなり、この両条件が整った細胞のみ破骨細胞へ分化することが可能となると考えられた。「まず骨が壊され，新しい骨が作られる」という骨恒常性機構における骨細胞とその膜小胞の一役を示す結果といえる。