Differential Expression Profiles of Long Noncoding RNA and mRNA of Osteogenically Differentiated Mesenchymal Stem Cells in Ankylosing Spondylitis
Differential Expression Profiles of Long Noncoding RNA and mRNA of Osteogenically Differentiated Mesenchymal Stem Cells in Ankylosing Spondylitis
复制标题
强直性脊柱炎成骨分化间充质干细胞长链非编码RNA和mRNA的差异表达谱
DOI：
10.3899/jrheum.151181
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发表时间：
2016-08-01
影响因子：
3.9
通讯作者：
Shen, Huiyong
中科院分区：
文献类型：
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作者：
Xie, Zhongyu;Li, Jinteng;Shen, Huiyong
目标。我们之前证明，来自强直性脊柱炎（AS； ASMSC）患者的间充质干细胞（MSC）比来自健康供体的间充质干细胞（HDMSC）具有更大的成骨分化能力，这种差异是AS病理性成骨的发病机制的基础。本研究比较了长链非编码RNA （lncRNA）和mRNA在成骨分化ASMSC和HDMSC中的表达水平，探讨了ASMSC成骨分化异常的确切机制。方法。用成骨分化培养基诱导HDMSC和ASMSC 10 d。然后通过芯片分析鉴定HDMSC和ASMSC之间lncRNA和mRNA的差异表达，然后进行生物信息学分析并通过定量实时荧光定量PCR （qRT-PCR）检测证实。此外，我们构建了编码-非编码基因共表达（CNC）网络来检测lncRNA与mRNA表达模式之间的关系。结果。与HDMSC相比，成骨分化ASMSC中共有520个lncRNA和665个mRNA差异表达。生物信息学分析显示64条信号通路存在显著差异，其中包括转化生长因子-β信号通路。qRT-PCR检测证实了芯片数据的可靠性。CNC网络显示，lnc-ZNF354A-1、lnc-LIN54-1、lnc-FRG2C-3、lnc-USP50-2等4种差异表达的lncRNA可能参与ASMSC成骨分化异常。结论。我们的研究表征了成骨分化ASMSC的lncRNA差异和mRNA表达谱，并鉴定出4个可能参与ASMSC异常成骨分化的lncRNA。这些结果为深入了解AS的病理性成骨的发病机制提供了依据。
Objective. We previously demonstrated that mesenchymal stem cells (MSC) from patients with ankylosing spondylitis (AS; ASMSC) have a greater osteogenic differentiation capacity than MSC from healthy donors (HDMSC) and that this difference underlies the pathogenesis of pathological osteogenesis in AS. Here we compared expression levels of long noncoding RNA (lncRNA) and mRNA between osteogenically differentiated ASMSC and HDMSC and explored the precise mechanism underlying abnormal osteogenic differentiation in ASMSC. Methods. HDMSC and ASMSC were induced with osteogenic differentiation medium for 10 days. Microarray analyses were then performed to identify lncRNA and mRNA differentially expressed between HDMSC and ASMSC, which were then subjected to bioinformatics analysis and confirmed by quantitative real-time PCR (qRT-PCR) assays. In addition, coding-non-coding gene co-expression (CNC) networks were constructed to examine the relationships between the lncRNA and mRNA expression patterns. Results. A total of 520 lncRNA and 665 mRNA were differentially expressed in osteogenically differentiated ASMSC compared with HDMSC. Bioinformatics analysis revealed 64 signaling pathways with significant differences, including transforming growth factor-β signaling. qRT-PCR assays confirmed the reliability of the microarray data. The CNC network indicated that 4 differentially expressed lncRNA, including lnc-ZNF354A-1, lnc-LIN54-1, lnc-FRG2C-3, and lnc-USP50-2 may be involved in the abnormal osteogenic differentiation of ASMSC. Conclusion. Our study characterized the differential lncRNA and mRNA expression profiles of osteogenically differentiated ASMSC and identified 4 lncRNA that may participate in the abnormal osteogenic differentiation of ASMSC. These results provide insight into the pathogenesis of pathological osteogenesis in AS.