title: Anti-apoptotic action of nerve growth factor in mouse osteoblastic cell line.
abstract: We investigated the potential role of nerve growth factor (NGF) in osteoblast survival in vitro. We found the expression of the mRNAs encoding NGF, brain-derived neurotrophic factor (BDNF), and trk-b, which is the receptor molecule of BDNF in mouse osteoblastic MC3T3-E1 cells. NGF high-affinity receptor trk-a was expressed continuously in the cells as visualized by Western blotting. A proinflammatory cytokine mixture stimulated NGF mRNA, and NGF protein release from MC3T3-E1 cells. When the effect of the nuclear factor-KB inhibitor pyrrolidine dithiocarbamate (PDTC) and activating protein-1 inhibitor curcumin were examined, a dose-dependent inhibition of cytokine-activated NGF expression occurred in the presence of PDTC or curcumin. Further, a specific inhibitor of p38 mitogen activated protein kinase (MAPK), i.e., SB203580, inhibited the induction of NGF in cytokines-treated cells in a dose-dependent manner whereas a specific inhibitor of classic MAPK, PD98059 had no effect on the induction of NGF. Treatment of anti-NGF IgG resulted in a potent increase of DNA fragmentation at a dose-dependent manner. NGF but not BDNF caused a dose-dependent reduction in the extent of apoptotic DNA breakdown under treatment with cytokines. Under similar conditions, the addition of NGF resulted in a potent reduction in bax protein but not in Fas, or bcl-xl. These findings demonstrated that NGF in non-neuronal osteoblastic cells may play an important role in cell survival as an anti-apoptotic factor.
authors.affiliation: Department of Pharmacology, School of Dentistry, Aichi-Gakuin University, Nagoya, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Mogi
authors.forename: A
authors.initials: A
authors.lastname: Kondo
authors.forename: K
authors.initials: K
authors.lastname: Kinpara
authors.forename: A
authors.initials: A
authors.lastname: Togari
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000235:genetics; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D016207:Cytokines / Q000494:pharmacology; D053938:DNA Fragmentation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000502:physiology; D020932:Nerve Growth Factor / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D020917:Receptor, trkA / Q000096:biosynthesis; D020813:Receptor, trkB / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013859:Thiocarbamates / Q000494:pharmacology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D016207:Cytokines; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D016328:NF-kappa B; D011725:Pyridines; D011759:Pyrrolidines; D012333:RNA, Messenger; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; D020932:Nerve Growth Factor; D020917:Receptor, trkA; D020813:Receptor, trkB; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one