Suppression of RANKL-induced osteoclast differentiation by cilostazol via SIRT1-induced RANK inhibition.

摘要: Abstract Osteoclasts are bone-specific multinucleated cells generated by differentiation of monocyte/macrophage hematopoietic lineages and degrade bone matrix secretion lytic enzymes. The regulation osteoclast provides a potential strategy for treatment bone-lytic damage. In this study, cilostazol, an inhibitor type III phosphodiesterase, inhibited RANKL [receptor activator nuclear factor kappa B (RANK) ligand]-induced RANK expression in marrow-derived precursors (BMMs) Raw 264.7 inhibiting PU.1 via SIRT1 activation. RANKL-induced was attenuated cilostazol rSIRT1 cells, these were blocked sirtinol. line with these, elevated mRNA protein levels 12–24 h increased activity, effects Furthermore, the PU.1, transcription required macrophage differentiation, suppressed cilostazol. Additionally, marked immunofluorescence staining rSIRT1, both attenuations prevented Extensive knee synovial tissues mouse model collagen-induced arthritis (CIA) markedly reduced (30 mg/kg/day). results, RANKL- M-CSF-induced BMMs to TRAP+ giant resorption pit formation associated decrease TRAP (a marker enzyme osteoclasts) activity. conclusion, activates SIRT1, which suppresses translocation thus, inhibits RANKL-stimulated causes anti-osteoclast vitro their murine CIA.