New regulatory system of RANK signaling via the binding of CCN2 and OPG

2014 Fiscal Year Final Research Report

• Project/Area Number: 25861755
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Functional basic dentistry
• Research Institution: Okayama University
• Principal Investigator: AOYAMA Eriko 岡山大学, 医歯(薬)学総合研究科, 助教 (10432650)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: OPG / RANK / CCN2 / osteoclast / bone marrow

Outline of Final Research Achievements

CCN2 is known as a modulator of other cytokines and receptors via direct molecular interactions with them. We screened additional factors binding to CCN2 and found that receptor activator of NF-kappa B (RANK) can bind to CCN2. RANK signaling is a critical in osteoclastogenesis. Notable affinity between CCN2 and RANK was confirmed by using surface plasmon resonance (SPR) analysis. In fact, CCN2 enhanced the RANK-mediated activation of NF-kappa B, p38 and JNK pathways, in RAW264. 7 cells; whereas CCN2 had no influence on RANK-RANK ligand (RANKL) binding. Moreover, CCN2 also significantly bound to osteoprotegerin (OPG), which is a decoy receptor of RANKL. Of note, OPG markedly inhibited the binding between CCN2 and RANK; and CCN2 cancelled the inhibitory effect of OPG on osteoclast differentiation. These findings suggest CCN2　as a fourth factor in the RANK/RANKL/OPG system for osteoclastogenesis, which regulates OPG and RANK via direct interaction.

Free Research Field

生化学