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

被引:25
作者
Baek, Jong Min [1 ]
Ahn, Sung-Jun [1 ]
Cheon, Yoon-Hee [2 ]
Lee, Myeung Su [3 ,5 ]
Oh, Jaemin [1 ,4 ,5 ]
Kim, Ju-Young [4 ]
机构
[1] Wonkwang Univ, Dept Anat, 344-2 Sinyong Dong, Iksan 570749, Jeonbuk, South Korea
[2] Wonkwang Univ, Ctr Metab Funct Regulat, Iksan 570749, South Korea
[3] Wonkwang Univ, Dept Internal Med, Div Rheumatol, Iksan 570749, South Korea
[4] Wonkwang Univ, Imaging Sci Based Lung & Bone Dis Res Ctr, 344-2 Sinyong Dong, Iksan 570749, Jeonbuk, South Korea
[5] Wonkwang Univ, Inst Skeletal Dis, Iksan 570749, Jeonbuk, South Korea
基金
新加坡国家研究基金会;
关键词
nicotinamide phosphoribosyltransferase; adipokine; osteoclast; osteoporosis; COLONY-ENHANCING FACTOR; CELLS; RANKL; BIOSYNTHESIS; PATHWAYS; PROTEINS; SURVIVAL; SIGNALS; MICE; FOS;
D O I
10.3892/mmr.2016.6069
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 mono nucleotide 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-kappa B ligand (RANKL)-induced osteoclastogenesis by decreasing the phosphorylation of various early signal transducers, including c-Jun N-terminal kinase, Akt, glycogen synthase kinase-3 beta, Bruton's tyrosine kinase and phospholipase C gamma-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.
引用
收藏
页码:784 / 792
页数:9
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