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首页> 外文期刊>Journal of Cellular Physiology >Functional role of Runx3 in the regulation of aggrecan expression during cartilage development
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Functional role of Runx3 in the regulation of aggrecan expression during cartilage development

机译：Runx3的调节功能的作用在软骨发育aggrecan表达式

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摘要

Runx2 and Runx3 are known to be expressed in the growth plate during endochondral bone formation. Here we addressed the functional role of Runx3 as distinct from Runx2 by using two models of postnatal bone repair: fracture healing that proceeds by an endochondral process and marrow ablation that proceeds by only an intramembranous process. Both Runx2 and Runx3 mRNAs were differentially up regulated during fracture healing. In contrast, only Runx2 showed increased expression after marrow ablation. During fracture healing, Runx3 was expressed earlier than Runx2, was concurrent with the period of chondrogenesis, and coincident with maximal aggrecan expression a protein associated with proliferating and permanent cartilage. Immunohistological analysis showed Runx3 protein was also expressed by chondrocytes in vivo. In contrast, Runx2 was expressed later during chondrocyte hypertrophy, and primary bone formation. The functional activities of Runx3 during chondrocyte differentiation were assessed by examining its regulatory actions on aggrecan gene expression. Aggrecan mRNA levels and aggrecan promoter activity were enhanced in response to the over-expression of either Runx2 and Runx3 in ATDC5 chondrogenic cell line, while sh-RNA knocked down of each Runx protein showed that only Runx3 knock down specifically suppressed aggrecan mRNA expression and promoter activity. ChIP assay demonstrated that Runx3 interactions were selective to sites within the aggrecan promoter and were only observed during early periods of chondrogenesis before hypertrophy. Our studies suggest that Runx3 positively regulates aggrecan expression and suggest that its function is more limited to cartilage development than to bone. In aggregate these data further suggest that the various members of the Runx transcription factors are involved in the coordination of chondrocyte development, maturation, and hypertrophy during endochondral bone formation.
机译：Runx2和Runx3表达生长板软骨内骨形成。我们称呼Runx3的功能作用有别于Runx2通过使用两个模型产后骨修复:骨折愈合收益由软骨内过程和骨髓消融,只有一个膜内的收益的过程。不同的监管在骨折愈合。骨髓消融后表达。比Runx2早疗愈,Runx3表达,并发软骨形成的时期,并与最大aggrecan表达一个重合蛋白和增殖有关永久的软骨。显示Runx3蛋白表达的也是软骨细胞在体内。表示以后在软骨细胞肥大,和初级骨形成。活动期间Runx3软骨细胞分化是通过检查其评估监管行为对aggrecan基因表达。Aggrecan mRNA水平和Aggrecan启动子活动在反应增强Runx2和Runx3表达的ATDC5 chondrogenic细胞系,sh-RNA撞倒的Runx蛋白质显示只有Runx3击倒特别压抑aggrecan mRNA表达和推广活动。芯片分析表明,Runx3交互选择性在aggrecan网站吗在早期启动子,只是观察前肥大软骨形成的时期。研究表明,Runx3积极调节aggrecan表达式,表明它的功能更有限的软骨发育比骨头。Runx的各个成员转录因子参与软骨细胞的协调发展,成熟,在软骨内肥大骨形成。

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