期刊
JOURNAL OF PERIODONTAL RESEARCH
卷 49, 期 5, 页码 563-573出版社
WILEY
DOI: 10.1111/jre.12136
关键词
antioxidant; deferoxamine; iron chelator; nuclear factor erythroid 2-related factor; osteoblastic dierentiation; periodontal ligament cells
资金
- National Research Foundation of Korea (NRF) - Korea government (MSIP) [2012R1A5A2051384]
- National Research Foundation of Korea [2012R1A5A2051384] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Background and Objective: Recently it was reported that deferoxamine (DFO), an iron chelator, stimulates bone formation from MG63 and mesenchymal stem cells, but inhibits differentiation in rat calvarial cells; however, the effect of DFO on osteoblastic differentiation in human periodontal ligament cells (hPDLCs) has not been reported. The aim of this study was to investigate the effects and the possible underlying mechanism of DFO on osteoblastic differentiation of hPDLCs. Material and Methods: The effect of DFO on osteoblast differentiation was determined by the staining intensity of calcium deposits with Alizarin red and by RT-PCR analysis of the expression of osteoblastic markers. Signal transduction pathways were analyzed by western blotting. Results: DFO increased osteogenic differentiation in a concentration-dependent manner by expression of the mRNA for differentiation markers and calcium nodule formation. Exposure of hPDLCs to DFO resulted in increases in the production of reactive oxygen species and in the levels of nuclear factor erythroid 2-related factor (Nrf2) protein in nuclear extractions, as well as a dose-dependent increase in the expression of Nrf2 target genes, including glutathione (GSH), glutathione S-transferase, c-glutamylcysteine lygase, glutathione reductase and glutathione peroxidase. Pretreatment with Nrf2 small interfering RNA, GSH depletion by buthionine sulfoximine and diethyl maleate, and with antioxidants by N-acetylcysteine and vitamin E, blocked DFO-stimulated osteoblastic differentiation. Furthermore, pretreatment with GSH depletion and antioxidants blocked DFO-induced p38 MAPK, ERK, JNK and nuclear factor-kappaB pathways. Conclusion: These data indicate, for the first time, that nontoxic DFO promotes osteoblastic differentiation of hPDLCs via modulation of the Nrf2-mediated antioxidant pathway.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据