Analysis of Regulatory Mechanism of RANK Gene Expression in Osteoclast Precursor Cells

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590461
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Ehime University
• Principal Investigator: KITAZAWA RIKO 愛媛大学, 医学部附属病院, 准教授 (00273780)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 破骨細胞 / RANK / 遺伝子プロモータ / 転写因子

Outline of Final Research Achievements

Osteoclasts are multinucleated giant cells specialized in bone resorption, and are the major therapeutic target in diseases such as Osteoporosis and metastatic bone tumor. Receptor activator of NF-κB (RANK) is a member of the tumor necrosis factor receptor (TNFR) family expressed in osteoclast precursors, and RANK-RANK ligand (RANKL) signaling is a key system for differentiation, during differentiation of bone marrow mono-nucleated cells into osteoclast precursors. We had cloned a 6-kb fragment containing the 5’-flanking region of the RANK gene and have analyzed the binding elements of transcription factors. RANK transcription was positively regulated by c-fos/AP-1. We have identified splicing variant of mouse and human RANK gene (vRANK) that contains an intervening exon between exons 1 and 2 of full-length RANK (fRANK) mRNA. Since this novel exon contains a stop codon, vRANK encodes short truncated amino acids. We have started to generate a vRANK-overexpressed transgenic mouse.

Free Research Field

病理学