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

Autor(es)

Wilches-Buitrago, L. ^{[1, 2]} ; Viacava, P. R. ^[1] ; Cunha, F. Q. ^[1] ; Alves-Filho, J. C. ^[1] ; Fukada, S. Y. ^[2]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, Ribeirao Preto - Brazil

^[2] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Phys & Chem, Ribeirao Preto - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Inflammation Research; v. 68, n. 5, p. 415-421, MAY 2019.
• Citações Web of Science: 0

Resumo

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 mu M). 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-kappa B activation was detected using RAW 264.7, stably expressing luciferase on the NF-B 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 v, NFATc1) by FBP correlates with a reduction of mineralized matrix resorption capacity. The mechanism underlying FBP-inhibition of osteoclastogenesis involves NF-kappa B/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. (AU)

• Processo FAPESP: 15/09034-0 - Efeito da O-GlcNAcilação sobre a osteoclastogênese e reabsorção óssea
• Beneficiário: Sandra Yasuyo Fukada Alves
• Linha de fomento: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/08216-2 - CPDI - Centro de Pesquisa em Doenças Inflamatórias
• Beneficiário: Fernando de Queiroz Cunha
• Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs