| Project/Area Number |
25293376
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Morphological basic dentistry
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| Research Institution | Meikai University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
SATO Takuya 明海大学, 歯学部, 講師 (00316689)
OKAYASU Mari 東京大学, 医学部付属病院, 特任臨床医 (10610941)
OGASAWARA Toru 東京大学, 医学部付属病院, 講師 (20359623)
SAWAMURA Tatsuya 信州大学, 医学部, 教授 (30243033)
ITO Junta 明海大学, 歯学部, 助教 (40609096)
HAYASHIDA Chiyomi 明海大学, 歯学部, 助教 (40710900)
KANEDA Toshio 星薬科大学, 薬学部, 講師 (70339521)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2015: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2013: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
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| Keywords | 炎症性骨破壊 / 破骨細胞 / 骨芽細胞 / LOX-1 / 破骨細胞形成 / 炎症性骨吸収 / 細胞融合 / RANKL産生 |
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| Outline of Final Research Achievements |
Lectin-like oxidized LDL receptor-1 (LOX-1) was downregulated with osteoclast (OC) differentiation. LOX-1 negatively regulates OC differentiation by suppressing the cell-cell fusion of preOC. The LOX-1-deleted (LOX-1-/-) mice consistently decreased the trabecular bone mass because of elevated bone resorption. In contrast, when the calvaria was inflamed by LPS-injection, the inflammation-induced bone destruction was reduced by LOX-1 deficiency. The expression of RANKL, a trigger molecule for OC differentiation, evoked by the inflammation was abrogated in the LOX-1-/- mice. Osteoblasts (OBs), the major RANKL producers, expressed LOX-1 in response to IL-1β and PGE2. In the co-culture of LOX-1-/- OBs and wild-type OC precursors, the osteoclastogenesis induced by IL-1β and PGE2 decreased in parallel with the downregulation of RANKL expression in OBs. Thus, LOX-1 abrogation results in resistance to inflammatory bone destruction, despite promoting osteoclastogenesis in the steady state.
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