Functional analysis of Siglec-15-DAP12 complex in osteoclast and bone metabolism.

2021 Fiscal Year Final Research Report

• Project/Area Number: 17K11008
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Nara Institute of Science and Technology
• Principal Investigator: Norihiro Ishida-Kitagawa 奈良先端科学技術大学院大学, 先端科学技術研究科, 助教 (30294284)
• Co-Investigator(Kenkyū-buntansha): 別所 康全 奈良先端科学技術大学院大学, 先端科学技術研究科, 教授 (70261253)
• Project Period (FY): 2017-04-01 – 2022-03-31
• Keywords: 骨代謝 / 破骨細胞 / シグナル伝達 / 免疫学 / 糖鎖

Outline of Final Research Achievements

ITAM-bearing protein DAP12 is essential for formation of bone resorbable mature osteoclasts, however critical DAP12-associated receptor for functional osteoclast formation was unclear. Our group previously reported that Siglec-15 is essential for formation of functional osteoclasts in concert with DAP12 in vitro and developed artificial protein revSSDKA which mimics Siglec-15-DAP12 complex as single polypeptide. In this research subject, it is found that revSSDKA which specifically expressed in osteoclasts rescued mild osteopetrotic phenotype found in both DAP12-null and Siglec-15-null mice. These achievements strongly suggested that Siglec-15 is necessary and sufficient DAP12-associated receptor for mature osteoclast formation.

Free Research Field

骨代謝

Academic Significance and Societal Importance of the Research Achievements

Siglec-15-DAP12複合体を一分子で模倣するタンパク質改良型SSDKAの破骨細胞特異的な発現がSiglec-15およびDAP12遺伝子欠損マウスの大理石骨病を回復するという本研究での成果は、Siglec-15が破骨細胞におけるDAP12会合受容体の実体であることを強く示唆する。これに基づきSiglec-15を標的として研究を進めることが、1）DAP12を介したシグナル系の制御メカニズムを解明する、また2）骨粗しょう症を始めとする骨疾患治療薬を開発する、などの学術的・社会的に意義のある課題に取り組む足がかりの一つになると考えられる。