| Project/Area Number |
23792487
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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 |
Periodontal dentistry
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| Research Institution | Kyushu Dental College (2012)
Showa University (2011) |
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Principal Investigator |
USUI Michihiko 九州歯科大学, 歯学部・歯周病学分野, 准教授 (10453630)
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| Co-Investigator(Renkei-kenkyūsha) |
SATO Tsuyoshi 埼玉医科大学, 歯学部, 講師 (60406494)
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| Project Period (FY) |
2011 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 歯肉上皮細胞 / RANKL / PKA signaling / 破骨細胞形成 / 歯肉上皮 / ＲＡＮＫＬ |
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| Research Abstract |
Periodontitis is a chronic inflammatory disease characterized by the destruction of alveolar bone. Receptor activator of nuclear factor kappa B ligand (RANKL) is known to be an essential factor for osteoclastogenesis. Recent clinical studies indicate that levels of RANKL in the gingival crevicular fluid are increased in periodontitis patients. Although the gingival sulcus is liend by gingival epithelial cells (GECs), RANKL expression in GECs is not fully understood. RT-PCR, western blotting and immunohistochemistry were performed to confirm RANKL expression in GECs and in gingival tissue. Ca9-22 cells, a human gingival epithelial cell line, were treated with tumor necrosis factor (TNF)-α, antibodies against TNF receptors, and an inhibitor and an activator of PKA signaling. The levels of RANKL expression were examined by real time PCR and western blotting. GECs and bone marrow-derived osteoclast precursors were co-cultured to examine the effect of GECs-produced RANKLon osteoclast formation. RANKL mRNA and protein were expressed in GECs. Immunohistochemistry also showed RANKL and TNF-α expression in gingival epithelium, but not in gingival connective tissue. TNF-α increased the levels of RANKL expression in GECs. TNF-α-induced RANKL expression was inhibited by antibody against TNF receptor type 1 (TNFR1) and an inhibitor of PKA signaling. GECs constitutively induced osteoclast formation. This effect was increased significantly by TNF-α and activator of PKA signaling, and prevented by RANK-Fc.TNF-α induces RANKL expression through PKA signaling in GECs, which regulate osteoclastogenesis. GECs may take part in progression of alveolar bone destruction by periodontitis.
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