Mechanism of the mitogenic effect of fluoride on osteoblast-like cells: evidences for a G protein-dependent tyrosine phosphorylation process

Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research
J CaverzasioJ P Bonjour

Abstract

Recent results indicate that a fluoroalumino complex (AlFx) is probably the molecule responsible for the mitogenic effect of fluoride in MC3T3-E1 osteoblast-like cells. Initial analysis suggested that a tyrosine phosphorylation (tyr phos) process similar to that induced by thrombin and activation of the p42 MAP kinase (ERK 2) mediate this cellular response. In the present study, the signaling mechanism activated by AlFx was further investigated. The results indicated that AlFx dose-dependently enhanced the tyr phos of the cell adhesion proteins FAK and paxillin, as well as of the adaptor molecules p46shc, p52shc, and p66shc and their association with GRB2. Pretreatment of MC3T3-E1 cells with cytochalasin D completely prevented FAK and paxillin tyr phos without any alteration in the tyr phos of Shc proteins and activation of ERK2 induced by AlFx. This observation suggests that in confluent MC3T3-E1 cells, there is no link between the activation of FAK induced by AlFx and the stimulation of ERK2. Pretreatment of the cells with pertussis toxin inhibited Shc phosphorylation, activation of ERK2, and markedly reduced cell replication induced by AlFx. This toxin also significantly reduced the stimulation of Pi transport activity induc...Continue Reading

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Citations

Nov 3, 1998·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·K H Lau, D J Baylink
Jan 26, 2000·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·A SuzukiJ Caverzasio
Sep 8, 2000·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·J CaverzasioJ P Bonjour
May 24, 2003·Critical Reviews in Oral Biology and Medicine : an Official Publication of the American Association of Oral Biologists·Liang Li
Jan 23, 2004·The Journal of Biological Chemistry·Takashi ShimoakaHiroshi Kawaguchi
Feb 19, 2004·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Kazuto HoshiHiroshi Kawaguchi
Nov 11, 2003·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·J GuicheuxJ Caverzasio
Jan 18, 2006·American Journal of Physiology. Lung Cellular and Molecular Physiology·Natalia V BogatchevaJoe G N Garcia
Jun 27, 2014·Journal of the Royal Society, Interface·Lindsey F DoughertyN Justin Marshall
Apr 22, 2011·British Journal of Pharmacology·Diane Gesty-Palmer, Louis M Luttrell
Feb 9, 2021·Mutation Research. Genetic Toxicology and Environmental Mutagenesis·Ana L H GarciaJuliana da Silva
May 9, 2002·Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology·Lucilia Pereira MourièsEvelyne Lopez
Jun 17, 1998·Bone·J CaverzasioJ P Bonjour
Aug 16, 2021·Pharmacology & Therapeutics·Eijiro JimiIchiro Nakamura

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