Department of Biomedical Sciences, Baylor College of Dentistry, Texas A&M University System Health Science Center, Dallas, Texas, USA.
FASEB J. 2010 Jun;24(6):1879-92. doi: 10.1096/fj.09-144659. Epub 2010 Feb 2.
Granulin epithelin precursor (GEP) has been implicated in development, tissue regeneration, tumorigenesis, and inflammation. Herein we report that GEP stimulates chondrocyte differentiation from mesenchymal stem cells in vitro and endochondral ossification ex vivo, and GEP-knockdown mice display skeleton defects. Similar to bone morphogenic protein (BMP) 2, application of the recombinant GEP accelerates rabbit cartilage repair in vivo. GEP is a key downstream molecule of BMP2, and it is required for BMP2-mediated chondrocyte differentiation. We also show that GEP activates chondrocyte differentiation through Erk1/2 signaling and that JunB transcription factor is one of key downstream molecules of GEP in chondrocyte differentiation. Collectively, these findings reveal a novel critical role of GEP growth factor in chondrocyte differentiation and the molecular events both in vivo and in vitro.
颗粒蛋白前体（GEP）在发育、组织再生、肿瘤发生和炎症中起作用。在此，我们报告称 GEP 可刺激体外间充质干细胞向软骨细胞分化和体外软骨内骨化，而 GEP 敲低小鼠则表现出骨骼缺陷。与骨形态发生蛋白（BMP）2 类似，重组 GEP 的应用可加速体内兔软骨修复。GEP 是 BMP2 的关键下游分子，是 BMP2 介导的软骨细胞分化所必需的。我们还表明，GEP 通过 Erk1/2 信号激活软骨细胞分化，JunB 转录因子是 GEP 在软骨细胞分化中的关键下游分子之一。总的来说，这些发现揭示了 GEP 生长因子在软骨细胞分化中的新的关键作用，以及体内和体外的分子事件。
