Kim Se Hwa, Cho Kyoung-Won, Choi Han Seok, Park Su Jin, Rhee Yumie, Jung Han-Sung, Lim Sung-Kil
Division of Endocrinology, Department of Internal Medicine, Kwandong University College of Medicine, Myongji Hospital, Goyang, Republic of Korea.
Biochem Biophys Res Commun. 2009 Aug 28;386(3):532-6. doi: 10.1016/j.bbrc.2009.06.071. Epub 2009 Jun 18.
The forkhead box C2 (Foxc2) protein is a member of the family of winged helix/forkhead transcription factors. Foxc2-deficient mice display defective formation of the aortic arches, multiple craniofacial bones, and vertebral columns. To investigate the role of Foxc2 in osteoblast differentiation, DNA containing Foxc2 was transfected into the developing cranial suture mesenchymal cells by electroporation. Compared to the controls, alkaline phosphatase (ALP) and bone sialoprotein were expressed strongly in suture mesenchymal cells in the Foxc2 overexpressed calvaria. After Foxc2-siRNA transfection, ALP staining was rarely observed in the suture mesenchyme and adjacent parietal bone of the calvaria. Meanwhile, overexpression of Foxc2 increased protein levels of beta-catenin and stimulated TCF/LEF transcriptional activity. The protein kinase A inhibitor H-89 suppressed Foxc2-mediated increases in TCF/LEF transcriptional activity (-40%, P<0.01). In conclusion, our results demonstrated that Foxc2 stimulated osteoblast differentiation of mesenchymal cells and preosteoblasts. Activation of canonical Wnt-beta-catenin signals might be involved in the Foxc2-mediated stimulation of osteoblast differentiation.
叉头框C2（Foxc2）蛋白是翼状螺旋/叉头转录因子家族的成员。Foxc2基因缺陷型小鼠表现出主动脉弓、多块颅面骨和脊柱的形成缺陷。为了研究Foxc2在成骨细胞分化中的作用，通过电穿孔将含有Foxc2的DNA转染到发育中的颅缝间充质细胞中。与对照组相比，碱性磷酸酶（ALP）和骨涎蛋白在Foxc2过表达的颅骨的缝间充质细胞中强烈表达。Foxc2-siRNA转染后，在颅骨的缝间充质和相邻顶骨中很少观察到ALP染色。同时，Foxc2的过表达增加了β-连环蛋白的蛋白水平并刺激了TCF/LEF转录活性。蛋白激酶A抑制剂H-89抑制了Foxc2介导的TCF/LEF转录活性的增加（-40%，P<0.01）。总之，我们的结果表明Foxc2刺激间充质细胞和成骨前体细胞的成骨细胞分化。经典Wnt-β-连环蛋白信号的激活可能参与了Foxc2介导的成骨细胞分化刺激。
