Elucidation of osteoclast differentiation by exosome isolated from mechanical stress-stimulated osteocyte.

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K11019
• 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): 2018-04-01 – 2021-03-31
• Keywords: メカニカルストレス / 骨細胞 / 破骨細胞分化 / 膜小胞 / 骨代謝 / マイクロRNA

Outline of Final Research Achievements

Osteocyte, which is the most abundant cell in bone tissues, is well known as a mechanical stress (MS) receiving cell. During bone remodelling, bone resorption by osteoclasts precedes bone formation by osteoblasts. However, its mechanism is still unknown. In this study, we examined whether exosome released from osteocyte by MS stimulation are involved in osteoclast differentiation.
Though the vesicles isolated from mechanical stress-loaded MLO-Y4 cells had no effect against osteoblast differentiation, these vesicles significantly induced osteoclast differentiation. To characterize the mechanisms by which mechanical stress-loaded MLO-Y4 cell vesicles induces osteoclast differentiation in murine macrophage RAW264.7 cells, we analysed vesicle membrane and vesicle internal proteins by nano-LC-MS/MS-based shotgun proteomics. As a result, Protein X , CD9 and CD63 were only detected in mechanical stress-loaded MLO-Y4 cell vesicles.

Free Research Field

健康科学

Academic Significance and Societal Importance of the Research Achievements

私たちが日常の生活活動する中で起きる骨代謝の基本機構である「まず骨が壊され，新しい骨が作られる」というホメオスタシス機構について様々な知見が報告されているが，未解明なところが多い。本研究では，成長期の体重増によるメカニカルストレスを受けた際の骨代謝時に骨細胞から分泌される膜小胞が深く関与していることを示すことができ，骨のホメオスタシス機構の一機構を明らかにできた点で学術的意義があった。また，骨代謝における膜小胞の役割（機能）を見出すことで，超高齢化社会の中で増える骨粗鬆症患者への治療薬への応用利用など発展性が期待できた点では社会的意義ある研究成果を導くことができたと考える。