The novel pro-osteogenic activity of NUCB2(1-83.).

The novel pro-osteogenic activity of NUCB2(1-83.).
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DOI:
10.1371/journal.pone.0061619
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Liu JN
Liu JN
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Li R;Wu Q;Zhao Y;Jin W;Yuan X;Wu X;Tang Y;Zhang J;Tan X;Bi F;Liu JN

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最近有报道称 NUCB21-83 是一种抑制食欲和抗高血糖的肽。在这里,我们报告 NUCB21-83 促进成骨。研究发现,每天一次静脉注射NUCB21-83两个月后,去势大鼠的股骨和腰椎骨密度增加。 NUCB21-83 还增加了小鼠 MC3T3-E1 前成骨细胞系的碱性磷酸酶活性并促进矿化。当 Arg60 和 Arg63 或 Ser72 都突变为 Ala 时,促成骨活性完全丧失,表明这些残基在结构上对其生物学功能很重要。此外,它还阻碍 RAW 264.7 巨噬细胞的破骨细胞分化。它还排除了由污染物或实验错误引起的影响的任何可能性,并证明观察到的促成骨活性是 NUCB21-83 本身的特定作用。这些发现表明,对 NUCB21-83 的进一步研究对于骨代谢疾病尤其是骨质疏松症的治疗具有重要价值。
NUCB21–83 has been recently reported as an anorexigenic and anti-hyperglycemic peptide. Here we report that NUCB21–83 promotes osteogenesis. It was found after two months of once-a-day intravenous injection of NUCB21–83, bone mineral density of femora and lumbar vertebrae were increased in ovariectomized rats. NUCB21–83 also increased the alkaline phosphatase activity and promoted mineralization in mouse MC3T3-E1 preosteoblastic cell line. When either both Arg60 and Arg63 or Ser72 were mutated to Ala, the pro-osteogenic activity was completely lost, indicating that these residues are structurally important for its biological function. Furthermore, it encumbered osteoclastic differentiation of RAW 264.7 macrophage. It also excluded any possibility of the effect caused by contaminants or experimental faults, and demonstrated that the pro-osteogenic activity observed was a specific effect of NUCB21–83 itself. These findings warranted that further studies on NUCB21–83 would be valuable for the treatment of bone metabolic diseases especially for osteoporosis.
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