Wnt/B-连环蛋白通路在 AIS 中的不对称表达：是原发性的还是继发性的？
Asymmetric Expression of Wnt/B-catenin Pathway in AIS: Primary or Secondary to the Curve?
机构信息
Department of Spine Surgery, Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
Joint Scoliosis Research Center of The Chinese University of Hong Kong and Nanjing University, Nanjing & Hong Kong, China.
出版信息
Spine (Phila Pa 1976). 2020 Jun 15;45(12):E677-E683. doi: 10.1097/BRS.0000000000003409.
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 the 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 three 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 three genes and Cobb angle.
CONCLUSION
There exists remar kably 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
研究设计
一项前瞻性病例对照研究。
目的
研究不对称改变是脊柱畸形的主要原因还是次要原因。
背景资料概要
先前的研究报告称，青少年特发性脊柱侧凸（AIS）患者的 Wnt/B-连环蛋白通路表达显著降低。迄今为止，尚无研究调查差异表达的 Wnt/B-连环蛋白通路与曲线起始之间的关系。
方法
从 40 名女性 AIS 患者和 20 名年龄匹配的先天性脊柱侧凸（CS）患者中采集椎旁肌肉。对于 CS 患者，样本采集自顶椎区的凹侧和凸侧。对于 AIS 患者，除了顶椎区外，还从脊柱近端双侧采集样本。使用 qPCR 和 Western blot 测定受 Wnt/B-连环蛋白通路调节的 LBX1、B-连环蛋白和 PAX3 的表达。使用 Student t 检验比较凹侧和凸侧的相对 mRNA 表达水平。采用 Pearson 相关分析确定基因表达与曲线幅度之间的关系。
结果
AIS 患者在顶椎区凹侧的 B-连环蛋白、LBX1 和 PAX3 的 mRNA 和蛋白表达明显低于凸侧。相比之下，在近端区域，这三个基因的 mRNA 表达相当。此外，CS 患者凹侧和凸侧之间的 mRNA 表达无显著差异。这三个基因的 mRNA 表达与 Cobb 角之间无显著相关性。
结论
AIS 患者在顶椎区存在明显的 Wnt/B-连环蛋白通路不对称表达，但 CS 患者顶椎区的表达无明显差异。进一步研究 Wnt/B-连环蛋白信号通路可能有助于揭示未来研究中 AIS 的病因。
证据等级
4 级。
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