...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research >The transcription factor paired box-5 promotes osteoblastogenesis through direct induction of Osterix and Osteocalcin
【24h】

The transcription factor paired box-5 promotes osteoblastogenesis through direct induction of Osterix and Osteocalcin

机译：配对的转录因子box-5通过直接诱导Osterix和Osteocalcin促进成骨细胞生成

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Although skeletal abnormalities are seen in mice deficient of particular paired box (Pax) family proteins, little attention has been paid to their role in osteoblastogenesis so far. Here, we investigated the possible involvement of several Pax family members in mechanisms underlying the regulation of differentiation and maturation of osteoblasts. Among different Pax family members tested, Pax5 was not markedly expressed in murine calvarial osteoblasts before culture, but progressively expressed by osteoblasts under differentiation toward maturation. Immunoreactive Pax5 was highly detectable in primary cultured mature osteoblasts on immunoblotting and in osteoblastic cells attached to cancellous bone in mouse tibial sections on immunohistochemistry, respectively. Knockdown by small interfering RNA (siRNA) of endogenous Pax5 led to significant inhibition of the expression of Osteocalcin, and Osterix through deterioration of gene transactivation, in addition to a1(I)Collagen expression and alkaline phosphatase (ALP) staining, without affecting runt-related transcription factor-2 (Runx2) expression and cell viability in osteoblastic MC3T3-E1 cells. The introduction of Pax5 enhanced promoter activities of Osteocalcin and Osterix in a manner dependent on the paired domain in MC3T3-E1 cells. Putative Pax5 binding sites were identified in the 5'-flanking regions of mouse Osteocalcin and Osterix, whereas chromatin immunoprecipitation assay revealed the direct binding of Pax5 to particular regions of Osteocalcin and Osterix promoters in MC3T3-E1 cells. Overexpression of Pax5 significantly increased Osteocalcin, Osterix, and a1(I)Collagen expression, ALP activity, and Ca2+ accumulation, without affecting Runx2 expression, in MC3T3-E1 cells. In vertebrae of transgenic mice predominantly expressing Pax5 in osteoblasts, a significant increase was seen in the ratio of bone volume over tissue volume and the bone formation rate. These findings suggest that Pax5 could positively regulate osteoblastic differentiation toward maturation in vitro, in addition to promoting bone formation and remodeling in vivo, as one of the transcription factors essential for controlling osteoblastogenesis independently of Runx2.
机译：尽管在缺乏特定配对盒（Pax）家族蛋白的小鼠中发现了骨骼异常，但迄今为止，它们在成骨细胞生成中的作用鲜为人知。在这里，我们调查了几个Pax家族成员可能参与了成骨细胞分化和成熟调控的机制。在测试的不同Pax家族成员中，Pax5在培养前在小鼠颅盖成骨细胞中未明显​​表达，但在向成熟分化的过程中由成骨细胞逐渐表达。免疫反应的Pax5在免疫培养的原代培养成骨细胞中免疫印迹和在小鼠胫骨切片中附着在松质骨上的成骨细胞中均可以检测到。内源性Pax5的小干扰RNA（siRNA）的敲低导致除a1（I）胶原蛋白表达和碱性磷酸酶（ALP）染色外，还通过破坏基因反式激活而显着抑制Osteocalcin和Osterix的表达，而不会影响矮小-成骨细胞MC3T3-E1细胞中相关转录因子2（Runx2）的表达和细胞活力。 Pax5的引入以依赖于MC3T3-E1细胞中配对结构域的方式增强了Osteocalcin和Osterix的启动子活性。在小鼠Osteocalcin和Osterix的5'侧翼区域中鉴定出推定的Pax5结合位点，而染色质免疫沉淀测定表明MC3T3-E1细胞中Pax5与Osteocalcin和Osterix启动子的特定区域直接结合。 Pax5的过表达在MC3T3-E1细胞中显着增加了骨钙素，Osterix和a1（I）胶原蛋白的表达，ALP活性以及Ca2 +的积累，而没有影响Runx2的表达。在成骨细胞中主要表达Pax5的转基因小鼠的椎骨中，发现骨体积比组织体积的比率和骨形成速率显着增加。这些发现表明，Pax5除了可以促进成骨和体内重塑之外，还可以在体外积极调节成骨细胞向成熟的分化，这是独立于Runx2来控制成骨细胞形成所必需的转录因子之一。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号