Nodal pathway genes are down-regulated in facial asymmetry.
Nodal pathway genes are down-regulated in facial asymmetry.
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DOI：
10.1097/scs.0000000000001076
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发表时间：
2014-11
期刊：
影响因子：
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通讯作者：
Sciote JJ
中科院分区：
文献类型：
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作者：
Nicot R;Hottenstein M;Raoul G;Ferri J;Horton M;Tobias JW;Barton E;Gelé P;Sciote JJ
摘要颜面不对称是颚畸形错合畸形患者常见的共病。错牙合畸形的遗传率正在迅速提高，但关于遗传对不对称的影响知之甚少。这项研究确定了在面部不对称患者中下调的关键不对称产生基因的表达差异。在BSSO正颌外科手术中采集咬肌样本，以纠正基于牙齿的错牙合畸形。患者被分类为II类或III类和开放或深咬错牙合伴或不伴面部不对称。肌肉样品在Affytechnic HT2.0微阵列全局表达芯片上分析基因表达差异。主成分分析结果显示，不对称患者与其他类型错畸形患者的基因表达差异有统计学意义（P<0.05）。我们确定了不同的节点信号通路（NSP），促进胚胎发生过程中的中胚层和内胚层和左右图案的发展。在不对称受试者中，Nodal和Lefty的表达增加了1.39-1.84倍（P<3.41×10−5），而整体膜调节因子Nomo 1、2、3的表达减少了-5.63至-5.81（P<3.05×10−4）。细胞内途径成员之间的倍数差异在-7.02至-2.47范围内为负（P<0.003）。最后，已知影响II型骨骼肌纤维大小的Nodal上游效应子Pitx 2在面部不对称中也显著降低（P<0.05）。当面部不对称是骨性错牙合的一部分时，咬肌中的NSP基因减少。这些数据表明，NSP下调，以帮助促进发展的不对称性。在这种情况下，Pitx 2表达差异也有助于骨骼和肌肉发育。
Facial asymmetry is a common comorbid condition in patients with jaw deformation malocclusion. Heritability of malocclusion is advancing rapidly, but very little is known regarding genetic contributions to asymmetry. This study identifies differences in expression of key asymmetry-producing genes which are down regulated in facial asymmetry patients. Masseter muscle samples were collected during BSSO orthognathic surgery to correct skeletal-based malocclusion. Patients were classified as Class II or III and open or deep bite malocclusion with or without facial asymmetry. Muscle samples were analyzed for gene expression differences on Affymetrix HT2.0 microarray global expression chips. Overall gene expression was different for asymmetric patients compared to other malocclusion classifications by principal component analysis (P<0.05). We identified differences in the nodal signaling pathway (NSP) which promotes development of mesoderm and endoderm and left-right patterning during embryogenesis. Nodal and Lefty expression was 1.39–1.84 fold greater (P<3.41×10−5) whereas integral membrane Nodal-modulators Nomo1,2,3 were −5.63 to −5.81 (P<3.05×10−4) less in asymmetry subjects. Fold differences among intracellular pathway members were negative in the range of −7.02 to −2.47 (P<0.003). Finally Pitx2, a upstream effector of Nodal known to influence the size of type II skeletal muscle fibers was also significantly decreased in facial asymmetry (P<0.05). When facial asymmetry is part of skeletal malocclusion there are decreases of NSP genes in masseter muscle. This data suggests that the NSP is down regulated to help promote development of asymmetry. Pitx2 expression differences also contributed to both skeletal and muscle development in this condition.