| Project/Area Number |
25861755
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Functional basic dentistry
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| Research Institution | Okayama University |
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Principal Investigator |
AOYAMA Eriko 岡山大学, 医歯(薬)学総合研究科, 助教 (10432650)
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | OPG / RANK / CCN2 / osteoclast / bone marrow / RANKL / CCN2/CTGF |
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| 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.
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