XBP1S, a BMP2-inducible transcription factor, accelerates endochondral bone growth by activating GEP growth factor.
XBP1S, a BMP2-inducible transcription factor, accelerates endochondral bone growth by activating GEP growth factor.
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XBP1S 是一种 BMP2 诱导型转录因子，通过激活 GEP 生长因子加速软骨内骨生长。
DOI：
10.1111/jcmm.12261
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发表时间：
2014-06
影响因子：
5.3
通讯作者：
Zhang P
中科院分区：
文献类型：
--
作者：
Guo FJ;Xiong Z;Han X;Liu C;Liu Y;Jiang R;Zhang P
我们之前报道过转录因子XBP1S结合RUNX2并通过作为RUNX2的辅助因子增强软骨细胞肥大。本文中，我们报道了XBP1S是BMP2的一个关键下游分子，是BMP2介导的软骨细胞分化所必需的。XBP1S在软骨细胞分化过程中上调，并在骨骼发育过程中呈现时空表达模式。XBP1S在体外刺激间充质干细胞的软骨细胞分化和体外软骨内成骨。此外，XBP1S激活颗粒上皮前体细胞（granulin- epithelial In precursor， GEP），这是一种已知的刺激软骨形成的生长因子，而内源性GEP是XBP1S刺激的软骨细胞肥大、矿化和软骨内骨形成所必需的，至少在一定程度上是必需的。此外，XBP1S促进gep刺激的软骨形成和软骨内骨形成。综上所述，这些发现表明bmp2诱导的转录因子XBP1S通过激活GEP软骨生长因子正向调节软骨内骨形成。
We previously reported that transcription factor XBP1S binds to RUNX2 and enhances chondrocyte hypertrophy through acting as a cofactor of RUNX2. Herein, we report that XBP1S is a key downstream molecule of BMP2 and is required for BMP2-mediated chondrocyte differentiation. XBP1S is up-regulated during chondrocyte differentiation and demonstrates the temporal and spatial expression pattern during skeletal development. XBP1S stimulates chondrocyte differentiation from mesenchymal stem cells in vitro and endochondral ossification ex vivo. In addition, XBP1S activates granulin-epithelin precursor (GEP), a growth factor known to stimulate chondrogenesis, and endogenous GEP is required, at least in part, for XBP1S-stimulated chondrocyte hypertrophy, mineralization and endochondral bone formation. Furthermore, XBP1S enhances GEP-stimulated chondrogenesis and endochondral bone formation. Collectively, these findings demonstrate that XBP1S, a BMP2-inducible transcription factor, positively regulates endochondral bone formation by activating GEP chondrogenic growth factor.