Fructose 1,6-bisphosphate inhibits osteoclastogenesis by attenuating RANKL-induced NF-κB/NFATc-1
| Autor: | Sandra Y. Fukada, José C. Alves-Filho, Fernando Q. Cunha, Paula Ramos Viacava, L. Wilches-Buitrago |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Fructose 1 6-bisphosphate Immunology Osteoclasts Bone Marrow Cells Osteoclast fusion 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Osteogenesis Fructosediphosphates Animals Luciferase Femur Viability assay Cells Cultured Pharmacology NFATC Transcription Factors Tibia biology FRUTOSE RANK Ligand NF-kappa B Cell Differentiation NF-κB Cell biology Resorption Mice Inbred C57BL 030104 developmental biology chemistry RANKL 030220 oncology & carcinogenesis biology.protein Signal transduction |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| ISSN: | 1420-908X 1023-3830 |
| DOI: | 10.1007/s00011-019-01228-w |
| Popis: | 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. 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. 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. Altogether these data show a protective role of a natural glycolytic intermediate in bone homeostasis that may have therapeutic benefit for osteolytic diseases. |
| Databáze: | OpenAIRE |
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