title: Nicotinamide phosphoribosyltransferase inhibits receptor activator of nuclear factor-κB ligand-induced osteoclast differentiation in vitro.
abstract: The adipokine nicotinamide phosphoribosyltransferase (Nampt), also known as pre-B-cell colony-enhancing factor or the insulin-mimetic hormone visfatin, has a crucial role in the conversion of nicotinamide to nicotinamide mononucleotide during biosynthesis of the coenzyme nicotinamide adenine dinucleotide. Previous reports have demonstrated the inhibitory effects of Nampt on osteoclast formation from human peripheral blood mononuclear cells and CD14+ monocytes. However, the effects of Nampt on bone marrow macrophage (BMM)‑derived osteoclastogenesis and its precise role in the process remain unclear. The present in vitro study used recombinant Nampt and BMMs as osteoclast precursors demonstrated that Nampt suppresses receptor activator of nuclear factor‑κB ligand (RANKL)‑induced osteoclastogenesis by decreasing the phosphorylation of various early signal transducers, including c‑Jun N‑terminal kinase, Akt, glycogen synthase kinase‑3 β, Bruton's tyrosine kinase and phospholipase C γ‑2. In addition, western blotting and reverse transcription‑quantitative polymerase chain reaction analysis indicated that Nampt downregulates the mRNA and protein expression levels of c‑Fos and nuclear factor of activated T cells, cytoplasmic 1, leading to a decrease in the expression of osteoclast‑specific genes including tartrate‑resistant acid phosphatase, osteoclast‑associated receptor and cathepsin K. However, the bone‑resorbing activity of mature osteoclasts treated with Nampt was similar to untreated control osteoclasts. This finding indicates that Nampt exerts its anti‑osteoclastogenic activity by targeting osteoclast precursor cells rather than mature osteoclasts. Consequently, the present study demonstrated that Nampt acts as a negative regulator of RANKL‑mediated differentiation of BMMs into osteoclasts, suggesting the potential therapeutic targets to treat bone-related disorders such as osteoporosis.
authors.affiliation: Department of Anatomy, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570‑749, Republic of Korea.
authors.forename: Jong Min
authors.initials: JM
authors.lastname: Baek
authors.affiliation: Department of Anatomy, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570‑749, Republic of Korea.
authors.forename: Sung-Jun
authors.initials: SJ
authors.lastname: Ahn
authors.affiliation: Department of Anatomy, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570‑749, Republic of Korea.
authors.forename: Yoon-Hee
authors.initials: YH
authors.lastname: Cheon
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Wonkwang University, Iksan, Jeonbuk 570‑749, Republic of Korea.
authors.forename: Myeung Su
authors.initials: MS
authors.lastname: Lee
authors.affiliation: Department of Anatomy, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570‑749, Republic of Korea.
authors.forename: Jaemin
authors.initials: J
authors.lastname: Oh
authors.affiliation: Imaging Science‑Based Lung and Bone Diseases Research Center, Wonkwang University, Iksan, Jeonbuk 570‑749, Republic of Korea.
authors.forename: Ju-Young
authors.initials: JY
authors.lastname: Kim
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation / Q000187:drug effects; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism; D054409:Nicotinamide Phosphoribosyltransferase / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D018950:Lipopolysaccharide Receptors; D050778:NFATC Transcription Factors; D016760:Proto-Oncogene Proteins c-fos; D053245:RANK Ligand; D011994:Recombinant Proteins; D016173:Macrophage Colony-Stimulating Factor; D054409:Nicotinamide Phosphoribosyltransferase; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D048031:JNK Mitogen-Activated Protein Kinases