Mechanism of Toll-like receptor-mediated bone disruption

• Project/Area Number: 21791802
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Morphological basic dentistry
• Research Institution: National Center for Geriatrics and Gerontology
• Principal Investigator: MORIWAKI Sawako 独立行政法人国立長寿医療研究センター, 遺伝子蛋白質解析室, 研究員 (90399593)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 口腔病理学 / Toll様受容体 / 菌体成分 / 破骨細胞

Research Abstract

Several Toll-like receptor(TLR) ligands including LPS are enhancer for pathological osteoclast formation. TLR2 ligand can induce osteoclast formation without any other osteoclastogenic factor. By contrast, TLR4 ligand is insufficient to induce osteoclast formation by itself. TLR4 signaling is composed of two pathways : MyD88-dependent pathway and TRIF/TRAM pathway associated with the introduction of IFN-inducible genes. Since it is considered that IFN-βwhich is generated by activation of TLR4 suppresses differentiation of osteoclast, we attempted to block the TRIF/TRAM pathway with various methods. However, ostoclastogenesis was not induced by TLR4 ligand stimulation. These results indicate the possibility that another unknown element is implicated in TLR4-dependent osteoclatstogenesis.