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Inflammation Research

, Volume 68, Issue 5, pp 415–421 | Cite as

Fructose 1,6-bisphosphate inhibits osteoclastogenesis by attenuating RANKL-induced NF-κB/NFATc-1

  • L. Wilches-Buitrago
  • P. R. Viacava
  • F. Q. Cunha
  • J. C. Alves-Filho
  • S. Y. FukadaEmail author
Original Research Paper
  • 102 Downloads

Abstract

Background

Although some glycolytic intermediates have been shown to modulate several cell type formation and activation, the functional role of fructose 1,6-bisphosphate (FBP) on osteoclastogenesis is still unknown.

Methods

Osteoclastogenesis was evaluated on bone marrow preosteoclasts cultured with M-CSF − 30 ng/ml, RANKL − 10 ng/ml, and two concentrations of FBP (100 and 300 µM). TRAP-positive stained cells were counted, and osteoclastogenic marker genes expression were evaluated by qPCR. Osteoclasts resorption capacity was evaluated by the expression of specific enzymes and capacity to resorb a mineralized matrix. The NF-κB activation was detected using RAW 264.7, stably expressing luciferase on the NF-κB responsive promoter.

Results

We show that FBP, the product of the first stage of glycolysis, inhibited RANKL-induced osteoclasts differentiation and TRAP activity. The treatment of preosteoclasts with FBP attenuated osteoclast fusion and formation, without affecting cell viability. Moreover, the inhibition of several osteoclastogenic marker genes expression (TRAP, OSCAR, DC-STAMP, Integrin αv, NFATc1) by FBP correlates with a reduction of mineralized matrix resorption capacity. The mechanism underlying FBP-inhibition of osteoclastogenesis involves NF-κB/NFATc1 signaling pathway inhibition.

Conclusion

Altogether these data show a protective role of a natural glycolytic intermediate in bone homeostasis that may have therapeutic benefit for osteolytic diseases.

Keywords

Bone remodeling Osteoclasts NFATc1 Fructose 1,6-bisphosphate 

Notes

Acknowledgements

The author’s thanks Mayara Santos Gomes for her technical assistance. This study was supported by grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP grant No. 2015/09034-0; 2013/08216-2) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq-130230/2016-2 scholarship to LWB).

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest.

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Ribeirao Preto Medical School, Department of PharmacologyUniversity of Sao PauloRibeirao PretoBrazil
  2. 2.School of Pharmaceutical Sciences of Ribeirao Preto, Department of Physics and ChemistryUniversity of Sao PauloRibeirao PretoBrazil

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