RRC ID 39544
Author Mogi M, Kondo A, Kinpara K, Togari A.
Title Anti-apoptotic action of nerve growth factor in mouse osteoblastic cell line.
Journal Life Sci.
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.
Volume 67(10)
Pages 1197-206
Published 2000
DOI 10.1016/s0024-3205(00)00705-0
PII S0024320500007050
PMID 10954053
MeSH Animals Apoptosis / physiology* Brain-Derived Neurotrophic Factor / biosynthesis Brain-Derived Neurotrophic Factor / genetics Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors Cytokines / pharmacology DNA Fragmentation / drug effects Enzyme Inhibitors / pharmacology Flavonoids / pharmacology Humans Imidazoles / pharmacology MAP Kinase Signaling System / drug effects MAP Kinase Signaling System / physiology Mice NF-kappa B / antagonists & inhibitors NF-kappa B / physiology Nerve Growth Factor / biosynthesis Nerve Growth Factor / genetics Nerve Growth Factor / physiology* Osteoblasts / cytology* Osteoblasts / drug effects Osteoblasts / metabolism Pyridines / pharmacology Pyrrolidines / pharmacology RNA, Messenger / biosynthesis RNA, Messenger / genetics RNA, Messenger / metabolism Receptor, trkA / biosynthesis Receptor, trkB / biosynthesis Reverse Transcriptase Polymerase Chain Reaction Thiocarbamates / pharmacology
IF 3.448
Times Cited 38
Human and Animal Cells