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Deferoxamine promotes osteoblastic differentiation in human periodontal ligament cells via the nuclear factor erythroid 2‐related factor‐mediated antioxidant signaling pathway
Author(s) -
Chung JH.,
Kim YS.,
Noh K.,
Lee YM.,
Chang SW.,
Kim EC.
Publication year - 2014
Publication title -
journal of periodontal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.31
H-Index - 83
eISSN - 1600-0765
pISSN - 0022-3484
DOI - 10.1111/jre.12136
Subject(s) - periodontal fiber , deferoxamine , signal transduction , microbiology and biotechnology , chemistry , cancer research , medicine , biology , dentistry
Background and Objective Recently it was reported that deferoxamine ( DFO ), an iron chelator, stimulates bone formation from MG 63 and mesenchymal stem cells, but inhibits differentiation in rat calvarial cells; however, the effect of DFO on osteoblastic differentiation in human periodontal ligament cells (h PDLC s) 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 h PDLC s. 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 h PDLC s 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 N rf2 target genes, including glutathione ( GSH ), glutathione S ‐transferase, γ‐glutamylcysteine lygase, glutathione reductase and glutathione peroxidase. Pretreatment with N rf2 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 ‐kappa B pathways. Conclusion These data indicate, for the first time, that nontoxic DFO promotes osteoblastic differentiation of h PDLC s via modulation of the N rf2‐mediated antioxidant pathway.