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.

Introduction
Materials and Methods
    1. Antibodies and reagents
    2. Mouse bone marrow-derived macrophagepreparation
    3. Osteoclast differentiation and tartrate-resistant acidphosphatase staining
    4. Western blot analysis
    5. Cell viability assay
    6. Statistical analysis
Results
    1. Visfatin induces osteoclast differentiation in BMDM
    2. Visfatin upregulates the expression of osteoclastassociatedmolecules
    3. Visfatin is upregulated during RANKL-inducedosteoclast differentiation
    4. FK866 attenuated visfatin-inducedosteoclastogenensis
    5. FK866 attenuated RANKL-inducedosteoclastogenensis
Discussion
Funding
Conflicts of Interest
References

• Chang Youp Ok(Department of Dental Pharmacology, School of Dentistry, Pusan National University, Yangsan 50612, Republic of Korea, Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan 50612, Republic of Korea)
• Soo-Kyung Bae(Department of Dental Pharmacology, School of Dentistry, Pusan National University, Yangsan 50612, Republic of Korea, Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan 50612, Republic of Korea) Corresponding author
• Hye-Ock Jang(Department of Dental Pharmacology, School of Dentistry, Pusan National University, Yangsan 50612, Republic of Korea)
• Moon-Kyoung Bae(Department of Oral Physiology, School of Dentistry, Pusan National University, Yangsan 50612, Republic of Korea)