Coupling regulation by osteoclastic exosomes

• Project/Area Number: 16H06261
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Orthopaedic surgery
• Research Institution: The University of Tokyo
• Principal Investigator: Kariya Yoshiaki 東京大学, 医学部附属病院, 助教 (20633168)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥24,050,000 (Direct Cost: ¥18,500,000、Indirect Cost: ¥5,550,000); Fiscal Year 2019: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2018: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2017: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000); Fiscal Year 2016: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
• Keywords: 骨リモデリング / 骨芽細胞 / カップリング / エクソソーム / 破骨細胞 / 細胞遊走 / 骨代謝 / 骨形成 / 細胞外膜小胞 / exosome / 骨・軟骨代謝 / 骨・軟骨代謝学

Outline of Final Research Achievements

We have revealed that exosome secreted from mature osteoclasts (OC exosome) has a function to regulate chemotactic ability of osteoblasts. Since our parallel researches have revealed that OC exosome can input RANKL reverse signaling, we checked the involvement of this signaling and have found that osteoblast chemotaxis is not regulated by RANKL reverse signaling. This result suggests that OC exosome contains multiple factors controlling bone remodeling related events and functions as a multi-functional unit. In addition, we have also revealed that OC exosome is localized to the periphery of bone resorption pits. Considering the spatiotemporal regulation of OC exosome secretion, it is suggested that OC exosome is a key regulator for the coupling from bone resorption to formation.

Academic Significance and Societal Importance of the Research Achievements

骨吸収と骨形成の反復（骨リモデリング）は骨量・骨質維持に重要である。本研究では、この骨吸収から骨形成へのカップリングに重要な因子として、破骨細胞が放出する細胞外膜小胞に注目した。これまでの研究および本研究成果をあわせると、破骨細胞由来細胞外膜小胞は、骨吸収から骨形成への移行を促す作用を細胞分化の点で制御するほか、骨芽細胞の運動性にも影響を与えていることが見出された。これらの成果は、膜小胞というタンパク質複合体が、複数細胞が関わる複雑なカップリング現象に関して多面的に関与していることを示しており、この膜小胞の更なる解明が骨代謝理解促進に重要であることを見出した学術的に意義深い研究である。

Research Products

• [Journal Article] Coupling of bone resorption and formation by RANKL reverse signalling. (2018)
  • Author(s): Ikebuchi Y, Aoki S, Honma M, Hayashi M, Sugamori Y, Khan M, Kariya Y, Kato G, Tabata Y, Penninger JM, Udagawa N, Aoki K, Suzuki H
  • Journal Title: Nature Volume: 561 Issue: 7722 Pages: 195-200
  • DOI: 10.1038/s41586-018-0482-7
  • Peer Reviewed / Open Access / Int'l Joint Research