Skip to main content

Advertisement

SpringerLink
Log in

Different Effects of Fluoride Exposure on the Three Major Bone Cell Types

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

Fluoride accumulates and is toxic to bones. Clinical bone lesions occur in a phased manner, being less severe early in the natural course of skeletal fluorosis. Previous research rarely focused on osteocyte, osteoclast, and osteoblast at the same time, although these three types of cells are involved in the process of fluorosis. In this study, commitment of bone cells was performed according to their respective characteristics. Osteocyte-like cells were verified by protein expression of sclerostin (SOST) in IDG-SW3 cell culture with mineral medium. Positive tartrate-resistant acid phosphatase (TRACP) staining, characteristic of osteoclasts, is observed in RAW264.7 cells after administration of RANKL. We successfully purified a high percentage (94%) of bone mesenchymal stem cells (BMSCs) co-expressing CD34 and CD44. Parallel studies were performed to observe cell viability and apoptosis rates in osteocyte, osteoclast, and osteoblast like cells by using MTT and Annexin V FITC assays. Our results demonstrated that osteocytes have a strong tolerance to high fluoride concentrations, while osteoclasts are more sensitive to changes of fluoride dose. The range of anabolic action of fluoride concentration on osteoblast was narrow. Notably, fluoride exposure aggravated apoptosis of osteocyte and osteoclast induced by administration of PTH and TGF-β, respectively. In short, three types of bone cells display disparate responses to fluoride exposure and to PTH- and TGF-β-induced apoptosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Brothwell D, Limeback H (2003) Breastfeeding is protective against dental fluorosis in a nonfluoridated rural area of Ontario, Canada. J Hum Lact 19:386–390

    Article  CAS  Google Scholar 

  2. Hellwig E, Lennon AM (2004) Systemic versus topical fluoride. Caries Res 38:258–262

    Article  CAS  Google Scholar 

  3. Bhawal UK, Lee HJ, Arikawa K, Shimosaka M, Suzuki M, Toyama T, Sato T, Kawamata R, Taguchi C, Hamada N, Nasu I, Arakawa H, Shibutani K (2015) Micromolar sodium fluoride mediates anti-osteoclastogenesis in Porphyromonas gingivalis-induced alveolar bone loss. Int J Oral Sci 7(4):242–249

    Article  CAS  Google Scholar 

  4. Fina BL, Lombarte M, Rigalli JP, Rigalli A (2014) Fluoride increases superoxide production and impairs the respiratory chain in ROS 17/2.8 osteoblastic cells. PLoS One 9(6):e100768

    Article  Google Scholar 

  5. Woo SM, Rosser J, Dusevich V, Kalajzic I, Bonewald LF (2011) Cell line IDG-SW3 replicates osteoblast-to-late-osteocyte differentiation in vitro and accelerates bone formation in vivo. J Bone Miner Res 26(11):2634–2646

    Article  CAS  Google Scholar 

  6. Cuetara BLV, Crotti TN, O'Donoghue AJ et al (2006) Cloning and characterization of osteoclast precursors from the RAW264.7 cell line. In Vitro Cell Dev Biol Anim 42(7):182–188

    Article  CAS  Google Scholar 

  7. Nadri S, Soleimani M (2007) Isolation murine mesenchymal stem cells by positive selection. Vitro Cell Dev Biol Anim 43(8–9):276–282

    Article  CAS  Google Scholar 

  8. Bonewald LF, Johnson ML (2008) Osteocytes, mechanosensing and Wnt signaling. Bone 42(4):606–615

    Article  CAS  Google Scholar 

  9. Xiong J, Onal M, Jilka RL, Weinstein RS, Manolagas SC, O'Brien CA (2011) Matrix-embedded cells control osteoclast formation. Nat Med 17:1235–1241

    Article  CAS  Google Scholar 

  10. Lundy MW, Stauffer M, Wergedal JE, Baylink DJ, Featherstone JDB, Hodgson SF, Riggs BL (1995) Histomophometric analysis of iliac crest bone biopsies in placebo-treated versus fluoride-treated subjects. Osteoporosis Int 5:115–129

    Article  CAS  Google Scholar 

  11. Chachra D, Turner CH, Dunipace AJ, Grynpas MD (1999) The effect of fluoride treatment on bone mineral in rabbits. Calcif Tissue Int 64(4):345–351

    Article  CAS  Google Scholar 

  12. 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(6):1067–1074

    Article  CAS  Google Scholar 

  13. Matsuda SS, Silva TL, Buzalaf MA, Rodrigues AC, de Oliveira RC (2014) Differential effects of fluoride during osteoblasts mineralization in C57BL/6J and C3H/HeJ inbred strains of mice. Biol Trace Elem Res 161(1):123–129

    Article  CAS  Google Scholar 

  14. Everett ET (2011) Fluoride's effects on the formation of teeth and bones, and the influence of genetics. J Dent Res 90(5):552–560

    Article  CAS  Google Scholar 

  15. Yu H, Jiang N, Yu X, Zhao Z, Zhang X, Xu H (2018) The role of TGF-β receptor 1-smad3 signaling in regulating the osteoclastic mode affected by fluoride. Toxicology 393:73–82

    Article  CAS  Google Scholar 

  16. Kaminsky LS, Mahoney MC, Leach J (1990) Fluoride: benefits and risks of exposure. Crit Rev Oral Biol Med 1:261–281

    Article  CAS  Google Scholar 

  17. Koide M, Kobayashi Y (2018) Regulatory mechanisms of sclerostin expression during bone remodeling. J Bone Miner Metab. https://doi.org/10.1007/s00774-018-0971-7

    Article  Google Scholar 

  18. Fulzele K, Dedic C, Lai F, Bouxsein M, Lotinun S, Baron R, Divieti Pajevic P (2018) Loss of Gsα in osteocytes leads to osteopenia due to sclerostin induced suppression of osteoblast activity. Bone 117:138–148

    Article  CAS  Google Scholar 

  19. Hayashi M, Nakashima T, Yoshimura N et al (2019) Autoregulation of osteocyte Sema3A orchestrates estrogen action and counteracts bone aging. Cell Metab S1550-4131(18):30758–30757

    Google Scholar 

  20. Bellido T, Saini V, Pajevic PD (2013) Effects of PTH on osteocyte function. Bone 54(2):250–257

    Article  CAS  Google Scholar 

  21. Houde N, Chamoux E, Bisson M, Roux S (2009) Transforming growth factor-beta1 (TGF-beta1) induces human osteoclast apoptosis by up-regulating Bim. J Biol Chem 284(35):23397–23404

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by the National Natural Science Foundation of China (grant number 81673111, Project “Study on role of osteocyte and PTH/TGF-beta signaling pathway in the mechanism of bone turnover occurred in skeletal fluorosis”), the Natural Science Foundation of Jilin Province of China (20180101151JC).

Funding

This study was funded by Project [Study on role of osteocyte and PTH/TGF-beta signaling pathway in the mechanism of bone turnover occurred in skeletal fluorosis] supported by National Natural Science Foundation of China (grant number 81673111) and by the Natural Science Foundation of Jilin Province of China (20180101151JC).

Author information

Authors and Affiliations

  1. School of Pharmaceutical Sciences, Jilin University, 1163 Xinmin Street, Changchun, Jilin Province, 130021, People’s Republic of China

    Ningning Jiang, Fengyang Guo, Xiuyun Zhang & Hui Xu

  2. China-Japan Union Hospital, Jilin University, Changchun, People’s Republic of China

    Boyao Sun

Authors
  1. Ningning Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fengyang Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Boyao Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiuyun Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hui Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hui Xu.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jiang, N., Guo, F., Sun, B. et al. Different Effects of Fluoride Exposure on the Three Major Bone Cell Types. Biol Trace Elem Res 193, 226–233 (2020). https://doi.org/10.1007/s12011-019-01684-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-019-01684-9

Keywords

Search

Navigation