Development of a novel osteoinductive factor using NELL1 proteins

2016 Fiscal Year Final Research Report

• Project/Area Number: 26350959
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biomolecular chemistry
• Research Institution: Nagoya University
• Principal Investigator: Niimi Tomoaki 名古屋大学, 生命農学研究科, 講師 (30377791)
• Co-Investigator(Renkei-kenkyūsha): KURODA Shun'ichi 大阪大学, 産業科学研究所, 教授 (60263406)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 骨分化 / 細胞接着 / 再生医療

Outline of Final Research Achievements

The NELL1 gene was originally identified in craniosynostosis patients as being specifically unregulated within prematurely fusing sutures. Because of its potent osteoinductive activity, NELL1 protein may be useful for bone regeneration therapy. However, there is little knowledge regarding NELL1 receptors and NELL1-mediated signaling pathways. In this study, we demonstrate that NELL1 binds to cell surface proteoglycans through its thrombospondin-1 N-terminal (TSPN) domain. Major heparin-binding sites were identified on the three-dimensional structural model of the TSPN domain of NELL1. Mutant analysis of the heparin-binding sites indicated that the heparin-binding activity of the TSPN domain is involved in interaction of NELL1 with cell surface proteoglycans. We also found that NELL1 binds to Robo3 receptor through its EGF-like repeats.

Free Research Field

分子細胞生物学