Elucidation of molecular mechanisms of Nrf2-mediated osteoclastogenesis and search of natural products as molecular targets

2015 Fiscal Year Final Research Report

• Project/Area Number: 25462892
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Functional basic dentistry
• Research Institution: Nagasaki University
• Principal Investigator: SAKAI Eiko 長崎大学, 医歯薬学総合研究科(歯学系), 助教 (10176612)
• Co-Investigator(Kenkyū-buntansha): TSUKUBA Takayuki 長崎大学, 医歯薬学総合研究科(歯学系), 教授 (30264055) ; OKAMOTO Kuniaki 長崎大学, 医歯薬学総合研究科(歯学系), 准教授 (10311846) ; NISHISHITA Kazuhisa 長崎大学, 医歯薬学総合研究科(歯学系), 助教 (20237697)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 破骨細胞 / 酸化ストレス / 天然物 / Nrf2 / 骨代謝

Outline of Final Research Achievements

This study investigated the role of Keap1/Nrf2 axis in the differentiation of osteoclast using wild-type, Keap1-deficient, and Nrf2-deficient mice. Keap1-deficient osteoclast precursors showed defects in osteoclastogenesis through the inhibition of phosphorylation of ERK, P38 MAPK, and JNK. Furthermore, the protein expression of NFATc1 was significantly downregulated. In contrast, Nrf2-deficient osteoclast precursors underwent enhanced osteoclastogenesis through the activation of ERK, p38 MAPK, and JNK signaling. Moreover, nuclear translocation of NFATc1 and c-Fos was increased in Nrf2-deficient osteoclast precursors. However, microcomputed tomographic analyses and histological analyses of femurs with hematoxylin-eosin staining showed no significant defects among these mice. Furthermore, we compared the inhibitory effects of cafestol and kahweol, or sanguiin H-6 and its degradation product, ellagic acid on osteoclast differentiation.

Free Research Field

歯科薬理学