Division of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of Dentistry, Aoba-ku, Sendai, Japan.
Dev Biol. 2011 Feb 15;350(2):337-47. doi: 10.1016/j.ydbio.2010.11.029. Epub 2010 Dec 11.
Fibroblast growth factors (FGF) are pluripotent growth factors that play pivotal roles in the development of various organs. During mandibular organogenesis, Meckel's cartilage, teeth, and mandibular bone differentiate under the control of various FGF. In the present study, we evaluated the role of FGF10 in rat mandibular chondrogenesis and morphogenesis using mandibular organ culture and mandibular cell micromass culture systems. The overexpression of Fgf10 induced by the electroporation of an FGF10 expression vector not only altered the size and shape of Meckel's cartilage, but also upregulated the expression of the cartilage characteristic genes Col2a1 and Sox9 in a mandibular organ culture system. Meckel's cartilage was deformed, and its size was increased when Fgf10 was overexpressed in the lateral area of the mandible. Meanwhile, no effect was found when Fgf10 was overexpressed in the medial portion. In the mandibular cell micromass culture, recombinant FGF10 treatment enhanced chondrogenic differentiation and endogenous ERK (extracellular signal-regulated kinase) phosphorylation in cells derived from the lateral area of the mandible. On the other hand, FGF10 did not have significant effects on mandibular cell proliferation. These results indicate that FGF10 regulates Meckel's cartilage formation during early mandibular morphogenesis by controlling the cell differentiation in the lateral area of the mandibular process in rats.
成纤维细胞生长因子 (FGF) 是多能生长因子,在各种器官的发育中起着关键作用。在颌骨器官发生过程中,下颌软骨、牙齿和下颌骨在各种 FGF 的控制下分化。在本研究中,我们使用下颌器官培养和下颌细胞微团培养系统,评估了 FGF10 在大鼠下颌软骨发生和形态发生中的作用。FGF10 表达载体的电穿孔诱导的 Fgf10 过表达不仅改变了 Meckel 软骨的大小和形状,而且在上颌器官培养系统中上调了软骨特征基因 Col2a1 和 Sox9 的表达。当 Fgf10 在下颌骨的外侧区域过表达时, Meckel 软骨变形,其大小增加。同时,当 Fgf10 在内侧区域过表达时,没有发现任何效果。在下颌细胞微团培养中,重组 FGF10 处理增强了来自下颌骨外侧区域的细胞的软骨分化和内源性 ERK(细胞外信号调节激酶)磷酸化。另一方面,FGF10 对下颌细胞增殖没有显著影响。这些结果表明,FGF10 通过控制大鼠下颌骨过程中外侧区域的细胞分化来调节早期下颌骨形态发生过程中的 Meckel 软骨形成。