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Differential Effects of Fluoride During Osteoblasts Mineralization in C57BL/6J and C3H/HeJ Inbred Strains of Mice

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Abstract

The behavior of fluoride ions in biological systems has advantages and problems. On one hand, fluoride could be a mitogenic stimulus for osteoblasts. However, high concentrations of this element can cause apoptosis in rat and mouse osteoblasts. Toward an understanding of this effect, we examined the role of sodium fluoride (NaF) in two mouse calvaria osteoblasts during the mineralization process. The animals used were C3H/HeJ (C3) and C57BL/6J (B6) mice. The calvaria cells were cultured for 28 days in the presence of several doses of NaF (0, 5, 10, 25, 50, and 75 μM), and we performed the assays: mineralized nodule measurements, alkaline phosphatase (ALP) activity, determination of type I collagen, and matrix metalloproteinase-2 (MMP-2) activity. The results showed no effects on alkaline phosphatase activity but decreased mineralized nodule formation. In B6 cells, the NaF effect was already seen with 10 μM of NaF and a greater increase of cellular type I collagen, and MMP-2 activity was upregulated after 7 days of NaF exposure. C3 osteoblasts showed a reduction in the mineralization pattern only after 50 μM of NaF with a slight increase of type I collagen and downregulation of MMP-2 activity during the mineralization period. In conclusion, fluoride affects the production and degradation of the extracellular matrix during early onset and probably during the mineralization period. Additionally, the genetic factors may contribute to the variation in cell response to fluoride exposure, and the differences observed between the two strains could be explained by an alteration of the bone matrix metabolism (synthesis and degradation).

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References

  1. Ringe JD (2002) Fluoride in osteoporosis. In: Bilezikian JP, Raisz LG, Rodan GA (eds) Principles of bone biology, 2nd edn. Academic, Orlando, pp 1387–1400

    Chapter  Google Scholar 

  2. Buzalaf MA, Caroselli EE, de Carvalho JG, Oliveira RC, da Silva Cardoso VE, Whitford GM (2005) Bone surface and whole bone as biomarkers for acute fluoride exposure. J Anal Toxicol 29:810–813

    Article  PubMed  Google Scholar 

  3. Gazzano E, Bergandi L, Riganti C, Aldieri E, Doublier S, Costamagna C, Bosia A, Ghigo D (2010) Fluoride effects: the two faces of janus. Curr Med Chem 17:2431–2441

    Article  PubMed  CAS  Google Scholar 

  4. Farley JR, Wergedal JE, Baylink DJ (1983) Fluoride directly stimulates proliferation and alkaline phosphatase activity of bone-forming cells. Science 222:330–332

    Article  PubMed  CAS  Google Scholar 

  5. Lau KH, Baylink DJ (1998) Molecular mechanism of action of fluoride on bone cells. J Bone Miner Res 13:1660–1667

    Article  PubMed  CAS  Google Scholar 

  6. Palmer C, Wolfe SH (2005) Position of the American Dietetic Association: the impact of fluoride on health. J Am Diet Assoc 105:1620–1628

    Article  PubMed  Google Scholar 

  7. Krishnamachari KA (1986) Skeletal fluorosis in humans: a review of recent progress in the understanding of the disease. Prog Food Nutr Sci 10:279–314

    PubMed  CAS  Google Scholar 

  8. Yan X, Feng C, Chen Q, Li W, Wang H, Lv L, Smith GW, Wang J (2009) Effects of sodium fluoride treatment in vitro on cell proliferation, apoptosis and caspase-3 and caspase-9 mRNA expression by neonatal rat osteoblasts. Arch Toxicol 83:451–458

    Article  PubMed  CAS  Google Scholar 

  9. Qu WJ, Zhong DB, Wu PF, Wang JF, Han B (2008) Sodium fluoride modulates caprine osteoblast proliferation and differentiation. J Bone Miner Metab 26:328–334

    Article  PubMed  CAS  Google Scholar 

  10. Ren G, Ferreri M, Wang Z, Su Y, Han B, Su J (2011) Sodium fluoride affects proliferation and apoptosis through insulin-like growth factor I receptor in primary cultured mouse osteoblasts. Biol Trace Elem Res 144:914–923

    Article  PubMed  CAS  Google Scholar 

  11. Li XN, Lv P, Sun Z, Li GS, Xu H (2014) Role of unfolded protein response in affecting osteoblast differentiation induced by fluoride. Biol Trace Elem Res 158:113–121

    Article  PubMed  CAS  Google Scholar 

  12. Waddington RJ, Langley MS (2003) Altered expression of matrix metalloproteinases within mineralizing bone cells in vitro in the presence of fluoride. Connect Tissue Res 44:88–95

    Article  PubMed  CAS  Google Scholar 

  13. Carvalho JG, Cestari TM, de Oliveira RC, Buzalaf MA (2008) Fluoride effects on ectopic bone formation in young and old rats. Methods Find Exp Clin Pharmacol 30:287–294

    Article  PubMed  Google Scholar 

  14. Zhou YL, Shi HY, Li XN, Lv P, Li GS, Liu QY, Xu H (2013) Role of endoplasmic reticulum stress in aberrant activation of fluoride-treated osteoblasts. Biol Trace Elem Res 154:448–456

    Article  PubMed  CAS  Google Scholar 

  15. Duan X, Xu H, Wang Y, Wang H, Li G, Jing L (2014) Expression of core-binding factor α1 and osteocalcin in fluoride-treated fibroblasts and osteoblasts. J Trace Elem Med Biol. doi:10.1016/j.jtemb.2014.02.004

    PubMed  Google Scholar 

  16. Fernandes MS, Yanai MM, Martins GM, Iano FG, Leite AL, Cestari TM, Taga R, Buzalaf MA, de Oliveira RC (2014) Effects of fluoride in bone repair: an evaluation of RANKL, OPG and TRAP expression. Odontology 102:22–30

    Article  CAS  Google Scholar 

  17. Waddington RJ, Embery G, Hall RC (1993) The influence of fluoride on proteoglycan structure using a rat odontoblast in vitro system. Calcif Tissue Int 52:392–398

    Article  PubMed  CAS  Google Scholar 

  18. Judex S, Donahue LR, Rubin C (2002) Genetic predisposition to low bone mass is paralleled by an enhanced sensitivity to signals anabolic to the skeleton. FASEB J 16:1280–1282

    PubMed  CAS  Google Scholar 

  19. Sheng MH, Lau KH, Beamer WG, Baylink DJ, Wergedal JE (2004) In vivo and in vitro evidence that the high osteoblastic activity in C3H/HeJ mice compared to C57BL/6J mice is intrinsic to bone cells. Bone 35:711–719

    Article  PubMed  CAS  Google Scholar 

  20. Slompo C, Buzalaf CP, Damante CA, Martins GM, Hannas AR, Buzalaf MA, Oliveira RC (2012) Fluoride modulates preosteoblasts viability and matrix metalloproteinases-2 and -9 activities. Braz Dent J 23:629–634

    Article  PubMed  Google Scholar 

  21. Viguet-Carrin S, Garnero P, Delmas PD (2006) The role of collagen in bone strength. Osteoporos Int 17:319–336

    Article  PubMed  CAS  Google Scholar 

  22. Yan D, Gurumurthy A, Wright M, Pfeiler TW, Loboa EG, Everett ET (2007) Genetic background influences fluoride’s effects on osteoclastogenesis. Bone 41:1036–1044

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  23. Yan D, Willett TL, Gu XM, Martinez-Mier EA, Sardone L, McShane L, Grynpas M, Everett ET (2011) Phenotypic variation of fluoride responses between inbred strains of mice. Cells Tissues Organs 194:261–267

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  24. Mousny M, Omelon S, Wise L, Everett ET, Dumitriu M, Holmyard DP, Banse X, Devogelaer JP, Grynpas MD (2008) Fluoride effects on bone formation and mineralization are influenced by genetics. Bone 43:1067–1074

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  25. Bellows CG, Aubin JE, Heersche JN (1993) Differential effects of fluoride during initiation and progression of mineralization of osteoid nodules formed in vitro. J Bone Miner Res 8:1357–1363

    Article  PubMed  CAS  Google Scholar 

  26. Kopp JB, Robey PG (1990) Sodium fluoride does not increase human bone cell proliferation or protein synthesis in vitro. Calcif Tissue Int 47:221–229

    Article  PubMed  CAS  Google Scholar 

  27. Chavassieux P, Chenu C, Valentin-Opran A, Delmas PD, Boivin G, Chapuy MC, Meunier PJ (1993) In vitro exposure to sodium fluoride does not modify activity or proliferation of human osteoblastic cells in primary cultures. J Bone Miner Res 8:37–44

    Article  PubMed  CAS  Google Scholar 

  28. Pan L, Shi X, Liu S, Guo X, Zhao M, Cai R, Sun G (2014) Fluoride promotes osteoblastic differentiation through canonical Wnt/β-catenin signaling pathway. Toxicol Lett 225:34–42

    Article  PubMed  CAS  Google Scholar 

  29. Caverzasio J, Palmer G, Bonjour JP (1998) Fluoride: mode of action. Bone 22:585–589

    Article  PubMed  CAS  Google Scholar 

  30. Chavassieux P, Boivin G, Serre CM, Meunier PJ (1993) Fluoride increases rat osteoblast function and population after in vivo administration but not after in vitro exposure. Bone 14:721–725

    Article  PubMed  CAS  Google Scholar 

  31. Chavassieux P, Pastoureau P, Boivin G, Chapuy MC, Delmas PD, Milhaud G, Meunier PJ (1991) Fluoride-induced bone changes in lambs during and after exposure to sodium fluoride. Osteoporos Int 2:26–33

    Article  PubMed  CAS  Google Scholar 

  32. Cerovic A, Miletic I, Sobajic S, Blagojevic D, Radusinovic M, El-Sohemy A (2007) Effects of zinc on the mineralization of bone nodules from human osteoblast-like cells. Biol Trace Elem Res 116:61–71

    Article  PubMed  CAS  Google Scholar 

  33. He YF, Ma Y, Gao C, Zhao GY et al (2013) Iron overload inhibits osteoblast biological activity through oxidative stress. Biol Trace Elem Res 152:292–296

    Article  PubMed  CAS  Google Scholar 

  34. Ozdemir S, Ayaz M, Can B, Turan B (2005) Effect of selenite treatment on ultrastructural changes in experimental diabetic rat bones. Biol Trace Elem Res 107:167–179

    Article  PubMed  CAS  Google Scholar 

  35. Robling AG, Turner CH (2002) Mechanotransduction in bone: genetic effects on mechanosensitivity in mice. Bone 31:562–569

    Article  PubMed  CAS  Google Scholar 

  36. Akhter MP, Cullen DM, Pedersen EA, Kimmel DB, Recker RR (1998) Bone response to in vivo mechanical loading in two breeds of mice. Calcif Tissue Int 63:442–449

    Article  PubMed  CAS  Google Scholar 

  37. Lau KH, Kapur S, Kesavan C, Baylink DJ (2006) Up-regulation of the Wnt, estrogen receptor, insulin-like growth factor-I, and bone morphogenetic protein pathways in C57BL/6J osteoblasts as opposed to C3H/HeJ osteoblasts in part contributes to the differential anabolic response to fluid shear. J Biol Chem 281:9576–9588

    Article  PubMed  CAS  Google Scholar 

  38. Baylink DJ, Finkelman RD, Mohan S (1993) Growth factors to stimulate bone formation. J Bone Miner Res 8(Suppl 2):S565–S572

    PubMed  Google Scholar 

  39. Tamura M, Nemoto E, Sato MM, Nakashima A, Shimauchi H (2010) Role of the Wnt signaling pathway in bone and tooth. Front Biosci 2:1405–1413

    Article  Google Scholar 

  40. Nair M, Belak ZR, Ovsenek N (2011) Effects of fluoride on expression of bone-specific genes in developing Xenopus laevis larvae. Biochem Cell Biol 89:377–386

    Article  PubMed  CAS  Google Scholar 

  41. Perumal E, Paul V, Govindarajan V, Panneerselvam L (2013) A brief review on experimental fluorosis. Toxicol Lett 223:236–251

    Article  PubMed  CAS  Google Scholar 

  42. Huo L, Liu K, Pei J et al (2013) Fluoride promotes viability and differentiation of osteoblast-like Saos-2 cells via BMP/Smads signaling pathway. Biol Trace Elem Res 155:142–149

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  43. Yan X, Yan X, Morrison A, Han T, Chen Q, Li J, Wang J (2011) Fluoride induces apoptosis and alters collagen I expression in rat osteoblasts. Toxicol Lett 200:133–138

    Article  PubMed  CAS  Google Scholar 

  44. Antonarakis GS, Moseley R, Waddington RJ (2014) Differential influence of fluoride concentration on the synthesis of bone matrix glycoproteins within mineralizing bone cells in vitro. Acta Odontol Scand. doi:10.3109/00016357.2014.882982

    PubMed  Google Scholar 

  45. Waddington RJ, Langley MS (1998) Structural analysis of proteoglycans synthesized by mineralizing bone cells in vitro in the presence of fluoride. Matrix Biol 17:255–268

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank Prof. Dr. Vinícius Carvalho Porto, head of the Centro Integrado de Pesquisa laboratories, and Mr. Ovidio Santos Sobrinho for their technical assistance. SSM was a recipient of fellowship from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) (06/54333-7). This work was supported by FAPESP 2010/02025-2.

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Authors and Affiliations

  1. Faculdade de Odontologia de Bauru, Departamento de Ciências Biológicas, Universidade de São Paulo, Alameda Dr. Octávio Pinheiro Brisolla, 9-75, Bauru, SP, 17012-901, Brazil

    Sandra S. Matsuda, Thelma L. Silva, Marília A. Buzalaf, Antonio C Rodrigues & Rodrigo Cardoso de Oliveira

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  1. Sandra S. Matsuda
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  2. Thelma L. Silva
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Correspondence to Rodrigo Cardoso de Oliveira.

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Matsuda, S.S., Silva, T.L., Buzalaf, M.A. et al. Differential Effects of Fluoride During Osteoblasts Mineralization in C57BL/6J and C3H/HeJ Inbred Strains of Mice. Biol Trace Elem Res 161, 123–129 (2014). https://doi.org/10.1007/s12011-014-0086-5

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  • DOI: https://doi.org/10.1007/s12011-014-0086-5

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