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Nicotinamide phosphoribosyltransferase inhibits receptor activator of nuclear factor-κB ligand-induced osteoclast differentiation in vitro

  • Authors:
    • Jong Min Baek
    • Sung‑Jun Ahn
    • Yoon‑Hee Cheon
    • Myeung Su Lee
    • Jaemin Oh
    • Ju‑Young Kim
  • View Affiliations / Copyright

    Affiliations: Department of Anatomy, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570‑749, Republic of Korea, Division of Rheumatology, Department of Internal Medicine, Wonkwang University, Iksan, Jeonbuk 570‑749, Republic of Korea, Imaging Science‑Based Lung and Bone Diseases Research Center, Wonkwang University, Iksan, Jeonbuk 570‑749, Republic of Korea
    Copyright: © Baek et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 784-792
    |
    Published online on: December 23, 2016
       https://doi.org/10.3892/mmr.2016.6069
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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.
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Copy and paste a formatted citation
Spandidos Publications style
Baek JM, Ahn SJ, Cheon YH, Lee MS, Oh J and Kim JY: Nicotinamide phosphoribosyltransferase inhibits receptor activator of nuclear factor-κB ligand-induced osteoclast differentiation in vitro. Mol Med Rep 15: 784-792, 2017.
APA
Baek, J.M., Ahn, S., Cheon, Y., Lee, M.S., Oh, J., & Kim, J. (2017). Nicotinamide phosphoribosyltransferase inhibits receptor activator of nuclear factor-κB ligand-induced osteoclast differentiation in vitro. Molecular Medicine Reports, 15, 784-792. https://doi.org/10.3892/mmr.2016.6069
MLA
Baek, J. M., Ahn, S., Cheon, Y., Lee, M. S., Oh, J., Kim, J."Nicotinamide phosphoribosyltransferase inhibits receptor activator of nuclear factor-κB ligand-induced osteoclast differentiation in vitro". Molecular Medicine Reports 15.2 (2017): 784-792.
Chicago
Baek, J. M., Ahn, S., Cheon, Y., Lee, M. S., Oh, J., Kim, J."Nicotinamide phosphoribosyltransferase inhibits receptor activator of nuclear factor-κB ligand-induced osteoclast differentiation in vitro". Molecular Medicine Reports 15, no. 2 (2017): 784-792. https://doi.org/10.3892/mmr.2016.6069
Copy and paste a formatted citation
x
Spandidos Publications style
Baek JM, Ahn SJ, Cheon YH, Lee MS, Oh J and Kim JY: Nicotinamide phosphoribosyltransferase inhibits receptor activator of nuclear factor-κB ligand-induced osteoclast differentiation in vitro. Mol Med Rep 15: 784-792, 2017.
APA
Baek, J.M., Ahn, S., Cheon, Y., Lee, M.S., Oh, J., & Kim, J. (2017). Nicotinamide phosphoribosyltransferase inhibits receptor activator of nuclear factor-κB ligand-induced osteoclast differentiation in vitro. Molecular Medicine Reports, 15, 784-792. https://doi.org/10.3892/mmr.2016.6069
MLA
Baek, J. M., Ahn, S., Cheon, Y., Lee, M. S., Oh, J., Kim, J."Nicotinamide phosphoribosyltransferase inhibits receptor activator of nuclear factor-κB ligand-induced osteoclast differentiation in vitro". Molecular Medicine Reports 15.2 (2017): 784-792.
Chicago
Baek, J. M., Ahn, S., Cheon, Y., Lee, M. S., Oh, J., Kim, J."Nicotinamide phosphoribosyltransferase inhibits receptor activator of nuclear factor-κB ligand-induced osteoclast differentiation in vitro". Molecular Medicine Reports 15, no. 2 (2017): 784-792. https://doi.org/10.3892/mmr.2016.6069
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