Asymmetric Expression of Wnt/B-catenin Pathway in AIS: Primary or Secondary to the Curve?
Asymmetric Expression of Wnt/B-catenin Pathway in AIS: Primary or Secondary to the Curve?
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DOI：
10.1097/brs.0000000000003409
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发表时间：
2020-02
期刊：
影响因子：
3
通讯作者：
Leilei Xu;Z. Dai;Chao Xia;Zhichong Wu;Zhenhua Feng;Xu Sun;Zhen Liu;Y. Qiu;J. Cheng;Ze-zhang Zhu
中科院分区：
文献类型：
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作者：
Leilei Xu;Z. Dai;Chao Xia;Zhichong Wu;Zhenhua Feng;Xu Sun;Zhen Liu;Y. Qiu;J. Cheng;Ze-zhang Zhu
研究设计：前瞻性病例对照研究。目的：研究脊柱畸形的不对称改变是原发性的还是继发性的。背景资料概述先前的研究报道了青少年特发性脊柱侧凸（AIS）患者中Wnt/B-连环蛋白通路的表达显著降低。迄今为止，缺乏研究差异表达的Wnt/B-catenin通路与曲线起始之间的关系。方法收集40例女性AIS患者和20例年龄匹配的先天性脊柱侧凸（CS）患者的椎旁肌。对于CS患者，从心尖区的凹侧和凸侧采集样本。对于AIS患者，除心尖区域外，还从脊柱的近端双侧采集样本。使用qPCR和蛋白质印迹来确定LBX 1、B-连环蛋白和PAX 3的表达，所有这些都由Wnt/B-连环蛋白途径调节。用Student t检验进行凹侧和凸侧之间的相对mRNA表达水平。Pearson相关分析用于确定基因表达与曲线幅度之间的关系。结果AIS患者心尖部凹侧B-catenin、LBX 1和PAX 3的mRNA和蛋白表达明显低于凸侧。相比之下，在近端区域，这3个基因的mRNA表达相当。CS患者凹侧和凸侧之间的mRNA表达无显著差异。3个基因的mRNA表达与Cobb角无明显相关性。结论Wnt/B-catenin信号通路在AIS的心尖部存在明显的不对称表达，而在CS患者的心尖部则无明显差异。对Wnt/B-catenin信号通路的深入研究有助于进一步揭示AIS的发病机制。证据等级4.
STUDY DESIGN A prospective case-control study. OBJECTIVES To investigate whether the asymmetric changes are primary or secondary to spinal deformity. SUMMARY OF BACKGROUND DATA Previous study reported significantly decreased expression of Wnt/B-catenin pathway in adolescent idiopathic scoliosis (AIS) patients. To date, there is a lack of study investigating the relationship between differentially expressed Wnt/B-catenin pathway and the onset of the curve. METHODS Paraspinal muscles were collected from 40 female AIS patients and 20 age-matched congenital scoliosis (CS) patients. For CS patients, the samples were collected from concave side and the convex side at the apical region. For AIS patients, the samples were collected from the proximal bilateral sides of the spine in addition to the apical region. qPCR and western blot were used to determine the expression of LBX1, B-catenin, and PAX3, all of which are regulated by the Wnt/B-catenin pathway. The relative mRNA expression level between the concave and the convex side was performed with the Student t test. Pearson correlation analysis was used to determine the relationship between gene expression and the curve magnitude. RESULTS AIS patients were found to have remarkably lower mRNA and protein expression of B-catenin, LBX1 and PAX3 in the concave side than in the convex side at the apical region. By contrast, at the proximal region, the mRNA expression of these 3 genes was comparable. Moreover, no significant difference regarding mRNA expression was found between the concave side and the convex side of CS patients. There was no remarkable correlation between the mRNA expression of the 3 genes and Cobb angle. CONCLUSIONS There exists remarkably asymmetric expression of Wnt/B-catenin pathway at the apical region of AIS, which however was comparable at the apical region of CS patients. Further investigation of Wnt/B-catenin signaling pathway may help reveal the etiology of AIS in future study. LEVEL OF EVIDENCE 4.