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首页> 外文期刊>Journal of Cellular Physiology >WNT4 acts downstream of BMP2 to mediate the regulation of ATRA signaling on RUNX1 expression: Implications for terminal differentiation of antler chondrocytes
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WNT4 acts downstream of BMP2 to mediate the regulation of ATRA signaling on RUNX1 expression: Implications for terminal differentiation of antler chondrocytes

机译:WNT4下游BMP2调解的行为ATRA信号调节RUNX1表达式:对终端分化的影响鹿茸软骨细胞

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Although ATRA is involved in regulating the proliferation and differentiation of chondrocytes, its underlying mechanism remains unknown. Here we showed that ATRA could stimulate the proliferation of antler chondrocytes and expression of COL X and MMP13 which were two well‐known markers for hypertrophic chondrocytes. Silencing of CRABP2 prevented the induction of ATRA on chondrocyte terminal differentiation, while overexpression of CRABP2 exhibited the opposite effects. CYP26A1 and CYP26B1 weakened the sensitivity of antler chondrocytes to ATRA. Further analysis evidenced that ATRA might induce chondrocyte terminal differentiation and modulate the expression of BMP2, WNT4, and RUNX1 through RARα/RXRα. Knockdown of BMP2 enhanced the induction of ATRA on the expression of COL X and MMP13, whereas overexpression of BMP2 abrogated this effectiveness. WNT4 might mediate the effects of ATRA and BMP2 on chondrocyte terminal differentiation. Dysregulation of BMP2 impaired the regulation of ATRA on WNT4 expression. Administration of ATRA to antler chondrocytes transfected with RUNX1 siRNA failed to induce the differentiation. Conversely, rRUNX1 strengthened the stimulation of ATRA on the expression of COL X and MMP13. Simultaneously, RUNX1 was a downstream effector of BMP2 and WNT4 in chondrocyte terminal differentiation. Moreover, WNT4 might play an important role in the crosstalk between BMP2 and RUNX1. Attenuation of BMP2 or WNT4 enhanced the interaction between ATRA and RUNX1, while constitutive expression of BMP2 or WNT4 reversed the regulation of ATRA on RUNX1. Collectively, WNT4 may act downstream of BMP2 to mediate the effects of ATRA on the terminal differentiation of antler chondrocytes through targeting RUNX1.
机译:尽管ATRA参与调控增殖和分化软骨细胞,其潜在的机制仍然存在未知的。鹿茸软骨细胞的增殖表达坳X和MMP13两个好认识标记肥厚性软骨细胞。沉默的CRABP2阻止的感应ATRA对软骨细胞终端分化,而过度CRABP2展出相反的效果。ATRA鹿茸软骨细胞的敏感性。进一步分析证明,ATRA诱导软骨细胞终端分化和调节BMP2的表达、WNT4 RUNX1通过RARα/ RXRα。ATRA诱导表达坳X和MMP13,而过度BMP2废除这个效果。ATRA和BMP2对软骨细胞的影响终端分化。ATRA的监管WNT4表达式。管理ATRA鹿茸软骨细胞转染RUNX1 siRNA未能诱导分化。ATRA的刺激坳的表达X和MMP13。下游效应器BMP2 WNT4软骨细胞终端分化。WNT4可能发挥重要作用相声BMP2和RUNX1之间。BMP2或WNT4增强之间的交互ATRA和RUNX1,组成型表达BMP2或WNT4逆转ATRA的规定RUNX1。BMP2调解ATRA对的影响终端鹿茸软骨细胞的分化通过针对RUNX1。

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