A distinct regulatory region of the Bmp5 locus activates gene expression following adult bone fracture or soft tissue injury.
A distinct regulatory region of the Bmp5 locus activates gene expression following adult bone fracture or soft tissue injury.
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DOI：
10.1016/j.bone.2015.04.010
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发表时间：
2015-08
期刊：
影响因子：
4.1
通讯作者：
Kingsley, David M.
中科院分区：
文献类型：
--
作者：
Guenther, Catherine A.;Wang, Zhen;Li, Emma;Tran, Misha C.;Logan, Catriona Y.;Nusse, Roel;Pantalena-Filho, Luiz;Yang, George P.;Kingsley, David M.
骨形态发生蛋白（BMPs）是骨和其他组织正常发育所需的关键信号分子。先前的研究表明，小鼠Bmp5基因的无效突变改变了发育过程中多种骨和软骨结构的大小、形状和数量。Bmp5突变也延迟了成年突变体肋骨骨折的愈合，这表明用于形成胚胎骨和软骨的相同信号在骨骼再生和修复过程中也被重复使用。尽管BMP在临床应用中作为刺激骨形成的试剂引起了强烈的兴趣，但对控制发育或损伤诱导的BMP表达的调控元件知之甚少。为了比较在胚胎骨形成和成年动物急性损伤后激活基因表达的DNA序列，我们测定了Bmp5基因周围区域刺激转基因小鼠lacZ报告基因表达的能力。分布在Bmp 5基因座上的多个基因组片段在正常发育期间（包括胚胎肋骨中）共同协调离散解剖结构域的表达。与此相反，一个独特的调控区激活表达肋骨骨折后，在成年动物。相同的损伤控制区域触发了胫骨骨折后间充质细胞、背部皮肤创伤后迁移的角质形成细胞和肺损伤后再生的上皮细胞中的基因表达。因此，Bmp5基因含有一个“损伤反应”控制区，它与胚胎增强子不同，并且在成年动物中被多种类型的损伤激活。
Bone morphogenetic proteins (BMPs) are key signaling molecules required for normal development of bones and other tissues. Previous studies have shown that null mutations in the mouse Bmp5 gene alter the size, shape and number of multiple bone and cartilage structures during development. Bmp5 mutations also delay healing of rib fractures in adult mutants, suggesting that the same signals used to pattern embryonic bone and cartilage are also reused during skeletal regeneration and repair. Despite intense interest in BMPs as agents for stimulating bone formation in clinical applications, little is known about the regulatory elements that control developmental or injury-induced BMP expression. To compare the DNA sequences that activate gene expression during embryonic bone formation and following acute injuries in adult animals, we assayed regions surrounding the Bmp5 gene for their ability to stimulate lacZ reporter gene expression in transgenic mice. Multiple genomic fragments, distributed across the Bmp5 locus, collectively coordinate expression in discrete anatomic domains during normal development, including in embryonic ribs. In contrast, a distinct regulatory region activated expression following rib fracture in adult animals. The same injury control region triggered gene expression in mesenchymal cells following tibia fracture, in migrating keratinocytes following dorsal skin wounding, and in regenerating epithelial cells following lung injury. The Bmp5 gene thus contains an “injury response” control region that is distinct from embryonic enhancers, and that is activated by multiple types of injury in adult animals.
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影响因子：
12.3
作者：
Berman BP;Pfeiffer BD;Laverty TR;Salzberg SL;Rubin GM;Eisen MB;Celniker SE
通讯作者：
Celniker SE
影响因子：
5.9
作者：
CHO, M;CHICHESTER, C;BUCKPITT, A
通讯作者：
BUCKPITT, A
影响因子：
3.1
作者：
Green, EL;McNutt, CW
通讯作者：
McNutt, CW
影响因子：
2.6
作者：
Ferguson, C;Alpern, E;Helms, JA
通讯作者：
Helms, JA
影响因子：
6.5
作者：
Gangnuss, S;Cowin, AJ;Rayner, TE
通讯作者：
Rayner, TE