Wang C, Zhang T, Liu W, Meng H, Song Y, Wang W
The First Affiliated Hospital of Harbin Medical University Department of Orthopedics Harbin China.
The Fourth Affiliated Hospital of Harbin Medical University Department of Neurosurgery Harbin China.
Cell Mol Biol (Noisy-le-grand). 2016 Feb 4;62(2):1-7.
Sox9 is a member of the high-mobility-group (HMG) box protein superfamily, which is expressed predominantly among cells in mesenchymal condensations during the early development of embryonic skeletons. The extracellular-signal-regulated kinase 5 (ERK5) is one of the mitogen-activated protein kinase (MAPK) family members of protein kinases. Roles for ERK5 signaling in the regulation of chondrogenesis and adult chondrocyte homeostasis have yet to be demonstrated. In this study, we found that ERK5 could down-regulate Col2al and Sox9 expression, and this down-regulation was inhibited by MEK5β, one of ERK5 inhibitor. Furthermore, we characterized the ERK5 response with the chromatin binding profile of Sox9 in MSCs in a genome-wide manner through an analysis of ChIP-seq data. This study will help to understand the interaction between the ERK5 and Sox9, and facilitate to decipher the mechanism of chondrogenesis in mesenchymal stem cells.
Sox9是高迁移率族(HMG)盒蛋白超家族的成员之一,在胚胎骨骼早期发育过程中主要在间充质凝聚中的细胞中表达。细胞外信号调节激酶5(ERK5)是丝裂原活化蛋白激酶(MAPK)家族的蛋白激酶成员之一。ERK5信号在软骨形成和成年软骨细胞稳态调节中的作用尚未得到证实。在本研究中,我们发现ERK5可下调Col2al和Sox9的表达,并且这种下调被ERK5抑制剂之一的MEK5β所抑制。此外,我们通过对ChIP-seq数据的分析,以全基因组方式表征了间充质干细胞中Sox9的染色质结合谱的ERK5反应。本研究将有助于理解ERK5与Sox9之间的相互作用,并有助于破译间充质干细胞中软骨形成的机制。