Ishibashi Osamu, Inui Takashi
Laboratory of Biological Macromolecules, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai 599-8531, Japan.
J Mol Signal. 2014 Jun 14;9:5. doi: 10.1186/1750-2187-9-5. eCollection 2014.
The periodontal ligament (PDL), connective tissue located between the cementum of teeth and alveolar bone of the mandibula, plays an important role in the maintenance and regeneration of periodontal tissues. We reported previously that endoglin was involved in the BMP-2-induced osteogenic differentiation of mouse PDL cells, which is associated with Smad-2 phosphorylation but not Smad-1/5/8 phosphorylation. In this study, to elucidate the detailed mechanism underlying the BMP-2 signalling pathway unique to PDL cells, we performed a microarray analysis to identify BMP-2-inducible genes in PDL-L2 cells, a mouse PDL-derived cell line, with or without endoglin knockdown.
Sixty-four genes were upregulated more than twofold by BMP-2 in PDL-L2 cells. Of these genes, 11 were endoglin-dependent, including Id4, which encodes ID4, a helix-loop-helix transcription factor closely associated with TGF-β signaling and osteoblast differentiation. The endoglin-dependent induction of ID4 by BMP-2 was also verified at a protein level.
Our findings indicate that ID4 could be a signal mediator involved in the BMP-2-induced endoglin-dependent osteogenic differentiation of PDL cells.
牙周韧带（PDL）是位于牙齿牙骨质与下颌骨牙槽骨之间的结缔组织，在牙周组织的维持和再生中发挥重要作用。我们之前报道过，内皮糖蛋白参与了骨形态发生蛋白-2（BMP-2）诱导的小鼠牙周韧带细胞的成骨分化，这与Smad-2磷酸化有关，但与Smad-1/5/8磷酸化无关。在本研究中，为了阐明牙周韧带细胞特有的BMP-2信号通路的详细机制，我们进行了微阵列分析，以鉴定在有或没有内皮糖蛋白敲低的情况下，小鼠牙周韧带来源的细胞系PDL-L2细胞中BMP-2诱导的基因。
在PDL-L2细胞中，64个基因被BMP-2上调了两倍以上。在这些基因中，11个是内皮糖蛋白依赖性的，包括Id4，它编码ID4，一种与转化生长因子-β信号传导和成骨细胞分化密切相关的螺旋-环-螺旋转录因子。BMP-2对ID4的内皮糖蛋白依赖性诱导在蛋白质水平也得到了验证。
我们的研究结果表明，ID4可能是参与BMP-2诱导的牙周韧带细胞内皮糖蛋白依赖性成骨分化的信号介质。
