Visfatin, an adipokine secreted by cells, is crucial for intracellular nicotinamide adenine dinucleotide+ biosynthesis. Extracellularly, visfatin plays diverse roles in inflammatory conditions, including obesity, which is closely linked to osteoclastogenesis. We previously showed that visfatin enhances receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclastogenesis in bone marrow-derived macrophages. However, its enzymatic activity during this process is poorly understood. Here, we investigated visfatin’s effects on RANKL-induced osteoclast differentiation. Our results demonstrate that visfatin promotes this differentiation, an effect inhibited by FK866, an inhibitor of visfatin’s enzymatic activity. Furthermore, FK866 also inhibited RANKL-induced osteoclast differentiation. These findings suggest that inhibiting visfatin’s enzymatic activity modulates osteoclast differentiation. Thus, visfatin plays an important role in osteoclastogenesis, both intracellularly and extracellularly, and FK866 has therapeutic potential for diseases characterized by imbalanced osteoclast formation, such as osteoporosis and periodontitis.

The fruit of Chaenomeles sinensis (Thouin) Koehne (Chaenomelis Fructus) known as “Mo-Gua” in Korea has been commonly used in traditional medicine to treat inflammatory diseases, such as sore throat. However, its effect on bone metabolism has not been elucidated yet. Here, we examined the effect of Chaenomelis Fructus ethanol extract (CFE) on receptor activator of nuclear factor (NF)-κB ligand (RANKL)-mediated osteoclast differentiation and formation. CF-E considerably inhibited osteoclast differentiation and tartrate-resistant acid phosphatase-positive multinuclear cell formation from bone marrow-derived macrophages and osteoclast precursor cells in a dose-dependent manner. In addition, the formation of actin rings and resorption pits were significantly suppressed in CF-E-treated osteoclasts as compared with the findings in non-treated control cells. Consistent with these phenotypic inhibitory results, the expressions of osteoclast differentiation marker genes (Acp5, Atp6v0d2 , Oscar, CtsK, and Tm7sf4) and Nfatc1 , a pivotal transcription factor for osteoclastogenesis, were markedly decreased by CF-E treatment. The inhibitory effect of CF-E on RANKL-induced osteoclastogenesis was associated with the suppression of NFATc1 expression, not by regulation of mitogen-activated protein kinases and NF-κB activation but by the inactivation of phospholipase C gamma 1 and 2. These results indicate that CF-E has an inhibitory effect on osteoclast differentiation and formation, and they suggest the possibility of CF-E as a traditional therapeutic agent against bone-resorptive diseases, such as osteoporosis, rheumatoid arthritis, and periodontitis.