Functional analysis of Siglec-15 in osteoclasts.

2017 Fiscal Year Final Research Report

• Project/Area Number: 26462295
• 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: Ishida-Kitagawa Norihiro 奈良先端科学技術大学院大学, バイオサイエンス研究科, 助教 (30294284)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Keywords: 骨・軟骨代謝学 / 破骨細胞 / 骨吸収 / NFATc1 / ITAM / 糖鎖 / シグナル伝達

Outline of Final Research Achievements

Signaling cascade through ITAM of DAP12 is essential for formation of functional osteoclasts. In this research, first we elucidated the functional amino acid sequence in cytoplasmic region of Siglec-15 and through this sequence microtubule related protein interacts with Siglec-15. From these findings, we constructed chimeric protein of Siglec-15 and DAP12 and found the expression of this artificial protein effectively rescued the phenotype of Siglec-15 KO mice in vitro. We established transgenic mice which express this chimeric protein in osteoclast specific manner and mate this mice with Siglec-15 KO mice which shows mild osteopetrosis as same as DAP12 KO mice. Finally, we could successfully obtain tibias and femurs from Siglec-15 KO background mice with or without transgenic allele.

Free Research Field

骨代謝学