A novel osteogenic helioxanthin-derivative acts in a BMP-dependent manner

A novel osteogenic helioxanthin-derivative acts in a BMP-dependent manner
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DOI:
10.1016/j.bbrc.2007.03.173
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发表时间:
2007-06-15
影响因子:
3.1
通讯作者:
Chung, Ung-il
Chung, Ung-il
中科院分区:
生物学4区
文献类型:
--
作者:
Ohba, Shinsuke;Nakajima, Keiji;Chung, Ung-il

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为了利用骨再生医学有效治疗严重的骨缺损,需要开发一种能有效诱导骨形成的小化合物。我们现在报告一种新的成骨helioxanthinderivatives, TH。TH诱导MC3T3-E1细胞、小鼠原代成骨细胞和小鼠胚胎干细胞成骨分化。TH与骨形态发生蛋白(bone morphogenetic protein, BMP) 2联合作用诱导原代成纤维细胞成骨标记基因mRNA表达和钙化。TH诱导dna结合1抑制剂(Id-1) mRNA表达,其成骨作用被Smad6或Noggin抑制。此外,TH诱导了Bmp4和Bmp6的mRNA表达。这些数据表明,TH通过增强现有bmp的作用和/或增加Bmp4和Bmp6的表达,以bmp依赖的方式发挥其强大的成骨作用。TH可能有助于建立一个更有效的骨再生系统。(c) 2007爱思唯尔公司版权所有。
To effectively treat serious bone defects using bone regenerative medicine, there is a need for the development of a small chemical compound that potently induces bone formation. We now report a novel osteogenic helioxanthin-derivative, TH. TH induced osteogenic differentiation in MC3T3-E1 cells, mouse primary osteoblasts, and mouse embryonic stem cells. The combination of TH and bone morphogenetic protein (BMP) 2 induced the mRNA expression of osteoblast marker genes and calcification in primary fibroblasts. The TH induced the mRNA of the inhibitor of DNA-binding 1 (Id-1), and its osteogenic effect was inhibited by Smad6 or Noggin. Furthermore, TH induced the mRNA expression of Bmp4 and Bmp6. These data suggest that TH exerts its potent osteogenic effect in a BMP-dependent manner by enhancing the effects of the existing BMPs and/or increasing the expression of Bmp4 and Bmp6. TH may help establish a more efficient bone regeneration system. (c) 2007 Elsevier Inc. All rights reserved.