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Journal ArticleDOI

NaF induces early differentiation of murine bone marrow cells along the granulocytic pathway but not the monocytic or preosteoclastic pathway in vitro.

01 May 2003-In Vitro Cellular & Developmental Biology – Animal (Springer-Verlag)-Vol. 39, Iss: 5, pp 243-248
TL;DR: It is suggested that NaF induces early differentiation of bone marrow hemopoietic progenitor cells along the granulocytic pathway but not the monoicytic pathway that is linked to osteoclast formation.
Abstract: The stimulatory effects of sodium fluoride (NaF) on bone formation have been explained solely, by its activation of osteoblasts. However, whether and how NaF acts on the osteoclast linearge is poorly understood. We previously found that NaF differentiates HL-60 cells to granulocytic cells. To further test this action, we have employed here primary cultures of progenitor cells derived from murine bone marrow. NaF at subtoxic concentations (<0.5 mM) significantly up-regulated activities of several intracellular enzymes (lactate dehydrogenase, β-glucuronidase, acid phosphatase), cellular reduction of nitroblue tetrazolium, and nitric oxide (NO) production; which are all accepted as general differentiation markers. NaF (<0.5 mM) also up-regulated granulocyte-specific markers (chloroacetate esterase, cell surface antigens[Mac-1, Gr-1]) but not any of the monocyte-specific markers (nonspecific esterase, cell surface antigens [F4/80, MOMA-2]). Although other general differentiation markers (phagocytosis, adhesion, appearance, nuclear:cytoplasmic ratio) were not appreciably influenced by NaF, essentially in support of our prevous data from HL-60 cells, the present findings suggest that NaF induces early differentiation of bone marrow hemopoietic progenitor cells along the granulocytic pathway but not the monoicytic pathway that is linked to osteoclast formation. Therefore, in addition to its potent stimulatory effects on osteoblastic bone formation, NaF applied to patients with osteoporosis could be expected to indirectly reduce osteoclastic bone resorption.
Citations
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Journal ArticleDOI
TL;DR: Genetic studies in mice are capable of identifying and characterizing fluoride-responsive genetic variations that can lead to the identification of at-risk human populations who are susceptible to the unwanted or potentially adverse effects of fluoride action and to the elucidation of fundamental mechanisms by which fluoride affects biomineralization.
Abstract: Fluorides are present in the environment. Excessive systemic exposure to fluorides can lead to disturbances of bone homeostasis (skeletal fluorosis) and enamel development (dental/enamel fluorosis). The severity of dental fluorosis is also dependent upon fluoride dose and the timing and duration of fluoride exposure. Fluoride's actions on bone cells predominate as anabolic effects both in vitro and in vivo. More recently, fluoride has been shown to induce osteoclastogenesis in mice. Fluorides appear to mediate their actions through the MAPK signaling pathway and can lead to changes in gene expression, cell stress, and cell death. Different strains of inbred mice demonstrate differential physiological responses to ingested fluoride. Genetic studies in mice are capable of identifying and characterizing fluoride-responsive genetic variations. Ultimately, this can lead to the identification of at-risk human populations who are susceptible to the unwanted or potentially adverse effects of fluoride action and to the elucidation of fundamental mechanisms by which fluoride affects biomineralization.

298 citations


Cites background from "NaF induces early differentiation o..."

  • ...Similar exposures of NaF ( 500 μM) can preferentially induce differentiation of primary outbred ddY mouse bone marrow cells along the granulocytic pathway in vitro (Oguro et al., 2003)....

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  • ...along the granulocytic pathway in vitro (Oguro et al., 2003)....

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Journal ArticleDOI
TL;DR: Fluoride has long been known to influence the activity of various enzymes in vitro as mentioned in this paper, with far-reaching consequences for our understanding of fundamental biological processes, and it has been demonstrated that many effects primarily attributed to fluoride are caused by synergistic action of fluoride plus aluminum.
Abstract: Fluoride has long been known to influence the activity of various enzymes in vitro. Later it has been demonstrated that many effects primarily attributed to fluoride are caused by synergistic action of fluoride plus aluminum. Aluminofluoride complexes have been widely used as analogues of phosphate groups to study phosphoryl transfer reactions and heterotrimeric G proteins involvement. A num- ber of reports on their use have appeared, with far-reaching consequences for our understanding of fundamental biological processes. Fluoride plus aluminum send false messages, which are amplified by processes of signal transduction. Many investigations of the long- term administration of fluoride to laboratory animals have demonstrated that fluoride and aluminofluoride complexes can elicit impair- ment of homeostasis, growth, development, cognition, and behavior. Ameliorative effects of calcium, vitamins C, D, and E have been re- ported. Numerous epidemiological, ecological, and clinical studies have shown the effects of fluoride on humans. Millions of people live in endemic fluorosis areas. A review of fluoride interactions from molecules to disease is necessary for a sound scientific assessment of health risks, which may be linked to the chronic intake of small doses of fluoride and aluminum from environmental and artificial sources.

60 citations

Journal ArticleDOI
TL;DR: Evidence examined in this review of the literature, and specifically the recent report by the National Research Council, offer strong support for an immediate reconsideration concerning risk vs benefit.
Abstract: Background: A review of the literature of the element fluorine and its bonded-form, fluoride, was undertaken. Generally regarded as safe, an expanding body of literature reveals that fluoride’s toxicity has been unappreciated, un-scrutinized, and hidden for over 70 years. The context for the literature search and review was an environmental climate-change study, which demonstrated widespread fluoride contamination by smokestack emissions from coal-fired electricity-generating plants. The objective of this review is to educate and inform regarding the ubiquitous presence and harmful nature of this now ever-present corrosive and reactive toxin. Methods: Methods include examination of national health agency reviews, primarily the National Research Council (NRC), Agency for Toxic Substances & Disease Registry (ATSDR), standard medical toxicology references, text books, as well as reports and documents from both private and public research as well as consumer-based NGOs. Study criteria were chosen for relevancy to the subject of the toxicity of fluoride. Results: Fluoride is the extreme electron scavenger, the most corrosive of all elements, as well as the most-reactive. Fluoride appears to attack living tissues, via several mechanisms. Fluoride renders strong evidence that it is a nonbiological chemical, demonstrating no observed beneficial function or role in organic chemistry, beyond use as a pesticide or insecticide. Fluorine has a strong role to play in industry, having been utilized extensively in metals, plastics, paints, aluminium, steel, and uranium production. Conclusion: Due to its insatiable appetite for calcium, fluorine and fluorides likely represent a form of chemistry that is incompatible with biological tissues and organ system functions. Based on an analysis of the affects of fluoride demonstrated consistently in the literature, safe levels have not been determined nor standardized. Mounting evidence presents conflicting value to its presence in biological settings and applications. Evidence examined in this review of the literature, and specifically the recent report by the National Research Council (NRC), offer strong support for an immediate reconsideration concerning risk vs benefit. Consensus recommendations from several sources are presented.

41 citations

Journal ArticleDOI
TL;DR: Evidence is presented that fluoride is an enzymatic poison, inducing oxidative stress, hormonal disruptions, and neurotoxicity, and that focusing the research on fluoride toxicity to the underlying integrative networks might contribute to unexpected epidemics in the future.
Abstract: Fluoride has been employed in laboratory investigations since the early 20th century. These studies opened the understanding of fluoride interventions to fundamental biological processes. Millions of people living in endemic fluorosis areas suffer from various pathological disturbances. The practice of community water fluoridation used prophylactically against dental caries increased concern of adverse fluoride effects. We assessed the publications on fluoride toxicity until June 2020. We present evidence that fluoride is an enzymatic poison, inducing oxidative stress, hormonal disruptions, and neurotoxicity. Fluoride in synergy with aluminum acts as a false signal in G protein cascades of hormonal and neuronal regulations in much lower concentrations than fluoride acting alone. Our review shows the impact of fluoride on human health. We suggest focusing the research on fluoride toxicity to the underlying integrative networks. Ignorance of the pluripotent toxic effects of fluoride might contribute to unexpected epidemics in the future.

33 citations

Journal ArticleDOI
01 Dec 2007-Bone
TL;DR: In conclusion, short term F treatment at physiological levels has strain-specific effects in mice and novel actions hallmarked by enhanced osteoclastogenesis shifts in hematopoietic cell differentiation in the C3H strain are demonstrated.

32 citations


Cites background from "NaF induces early differentiation o..."

  • ...At modest concentrations (b500 μM), NaF has been shown to promote differentiation of the human promyelocytic tumor cells (HL-60) to granulocytelike cells and induce differentiation of mouse bone marrow cells along the granulocytic pathway in vitro [36,37]....

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References
More filters
Journal Article
TL;DR: Testing as a sole agent, IFN-gamma was the only one of the 12 cytokines capable of inducing both NO2- and H2O2 release and the pathways leading to secretion of H2 O2 and No2- are independent.
Abstract: The capacity of 12 cytokines to induce NO2- or H2O2 release from murine peritoneal macrophages was tested by using resident macrophages, or macrophages elicited with periodate, casein, or thioglycollate broth. Elevated H2O2 release in response to PMA was observed in resident macrophages after a 48-h incubation with IFN-gamma, TNF-alpha, TNF-beta, or CSF-GM. Of these, only IFN-gamma induced substantial NO2- secretion during the culture period. The cytokines inactive in both assays under the conditions tested were IL-1 beta, IL-2, IL-3, IL-4, IFN-alpha, IFN-beta, CSF-M, and transforming growth factor-beta 1. Incubation of macrophages with IFN-gamma for 48 h in the presence of LPS inhibited H2O2 production but augmented NO2- release, whereas incubation in the presence of the arginine analog NG-monomethylarginine inhibited NO2- release but not H2O2 production. Although neither TNF-alpha nor TNF-beta induced NO2- synthesis on its own, addition of either cytokine together with IFN-gamma increased macrophage NO2- production up to six-fold over that in macrophages treated with IFN-gamma alone. Moreover, IFN-alpha or IFN-beta in combination with LPS could also induce NO2- production in macrophages, as was previously reported for IFN-gamma plus LPS. These data suggest that: 1) tested as a sole agent, IFN-gamma was the only one of the 12 cytokines capable of inducing both NO2- and H2O2 release; 2) the pathways leading to secretion of H2O2 and NO2- are independent; 3) either IFN-gamma and TNF-alpha/beta or IFN-alpha/beta/gamma and LPS can interact synergistically to induce NO2- release.

2,829 citations


"NaF induces early differentiation o..." refers methods in this paper

  • ...…amount of nitric oxide (NO) (as assessed by NO22) released into culture media of cells stimulated by lipopolysaccaride (LPS) (Escherichia coli O111: B4) (1 mg/ml for the last 24 h; DIFCO) by the method of Ding et al. (1988) using the Griess reagents (Dojin Chemical Laboratories, Kumamoto, Japan)....

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Journal ArticleDOI
04 Apr 1986-Science
TL;DR: Experiments were conducted to isolate and characterize the gene and gene product of a human hematopoietic colony-stimulating factor with pluripotent biological activities, which has the ability to induce differentiation of a murine myelomonocytic leukemia cell line WEHI-3B(D+) and cells from patients with newly diagnosed acute nonlymphocytic cancer.
Abstract: Experiments were conducted to isolate and characterize the gene and gene product of a human hematopoietic colony-stimulating factor with pluripotent biological activities. This factor has the ability to induce differentiation of a murine myelomonocytic leukemia cell line WEHI-3B(D+) and cells from patients with newly diagnosed acute nonlymphocytic leukemia (ANLL). A complementary DNA copy of the gene encoding a pluripotent human granulocyte colony-stimulating factor (hG-CSF) was cloned and expressed in Escherichia coli. The recombinant form of hG-CSF is capable of supporting neutrophil proliferation in a CFU-GM assay. In addition, recombinant hG-CSF can support early erythroid colonies and mixed colony formation. Competitive binding studies done with 125I-labeled hG-CSF and cell samples from two patients with newly diagnosed human leukemias as well as WEHI-3B(D+) cells showed that one of the human leukemias (ANLL, classified as M4) and the WEHI-3B(D+) cells have receptors for hG-CSF. Furthermore, the murine WEHI-3B(D+) cells and human leukemic cells classified as M2, M3, and M4 were induced by recombinant hG-CSF to undergo terminal differentiation to macrophages and granulocytes. The secreted form of the protein produced by the bladder carcinoma cell line 5637 was found to be O-glycosylated and to have a molecular weight of 19,600.

1,289 citations


"NaF induces early differentiation o..." refers background or methods or result in this paper

  • ...As demonstrated elsewhere (Stanley et al., 1983; Souza et al., 1986), in our positive controls,...

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  • ...The cells treated with G-CSF (100 ng/ml) (kindly supplied by Chugai Pharmaceutical Co., Tokyo, Japan) were used as a positive control for granulocytic differentiation (Souza et al., 1986)....

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  • ...As demonstrated elsewhere (Stanley et al., 1983; Souza et al., 1986), in our positive controls, M-CSF (100 U/ml) and G-CSF (100 ng/ml) up-regulated Mac-1 (246% of control) and Gr-1 (260% of control), respectively (Fig....

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Journal ArticleDOI
01 Jan 1982-Cell
TL;DR: A method is described for the production of a highly purified and homogeneous population of adherent bone marrow-derived macrophages that are devoid of CSF-1-producing cells, and the method may also be used to obtain nonadherent precursors of the mononuclear phagocytic series.

653 citations

Journal ArticleDOI
21 Oct 1983-Science
TL;DR: Treatment with sodium fluoride increased proliferation and alkaline phosphatase activity of bone cells in vitro and increasedBone formation in embryonic calvaria at concentrations that stimulate bone formation in vivo.
Abstract: Fluoride is one of the most potent but least well understood stimulators of bone formation in vivo. Bone formation was shown to arise from direct effects on bone cells. Treatment with sodium fluoride increased proliferation and alkaline phosphatase activity of bone cells in vitro and increased bone formation in embryonic calvaria at concentrations that stimulate bone formation in vivo.

576 citations


"NaF induces early differentiation o..." refers background or result in this paper

  • ...The cellular and molecular basis of this application has been explained solely by the evidence that fluoride stimulates osteoblastic proliferation and bone formation in vivo and in vitro (Briacon and Meunier, 1981; Farley et al., 1983, 1988; Lau et al., 1989; Chavassieux, 1990; Kawase et al., 1991)....

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  • ...This result differs from published data, suggesting that NaF may act as a mitogen on osteoblastic cells (Farley et al., 1983; Kawase et al., 1991)....

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  • ...NaF may act as a mitogen on osteoblastic ceils (Farley et al., 1983; Kawase et al., 1991)....

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  • ...…osteoporosis, NaF at appropriate concentrations increases bone mass not only by stimulating osteoblastic bone formation (Briacon and Meunier, 1981; Farley et al., 1983, 1988; Lau et al., 1989; Chavassieux, 1990; Kawase et al., 1991) but also probably by suppressing the development of osteoclasts…...

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Journal ArticleDOI

510 citations


"NaF induces early differentiation o..." refers background or methods in this paper

  • ...Cell viability in cultures treated with M-CSF (100 U/ml), a known hemopoietic growth factor (Tushinski et al., 1982; Stanley et al., 1983), decreased with d of culture until day 4 (61% of control), but further predicted decrease was suppressed on day 6 (68% of control), indicating that cell replication is possibly stimulated (Fig....

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  • ...As demonstrated elsewhere (Stanley et al., 1983; Souza et al., 1986), in our positive controls, M-CSF (100 U/ml) and G-CSF (100 ng/ml) up-regulated Mac-1 (246% of control) and Gr-1 (260% of control), respectively (Fig....

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  • ...Macrophage colony–stimulating factor (100 U/ml) (Genzyme, Cambridge, MA) was used as a positive control (Tushinski et al., 1982; Stanley et al., 1983)....

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  • ...Cell viability in cultures treated with M-CSF (100 U/ml), a known hemopoietic growth factor (Tushinski et al., 1982; Stanley et al., 1983), decreased with d of culture until day 4 (61% of control), but further predicted decrease was suppressed on day 6 (68% of control), indicating that cell…...

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