Identification of Differential Genes Expression Profiles and Pathways of Bone Marrow Mesenchymal Stem Cells of Adolescent Idiopathic Scoliosis Patients by Microarray and Integrated Gene Network Analysis
Identification of Differential Genes Expression Profiles and Pathways of Bone Marrow Mesenchymal Stem Cells of Adolescent Idiopathic Scoliosis Patients by Microarray and Integrated Gene Network Analysis
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微阵列和整合基因网络分析鉴定青少年特发性脊柱侧凸患者骨髓间充质干细胞的差异基因表达谱和通路
作者：
仉建国
研究设计。微阵列方法和综合基因网络分析。客观的。探讨特发性脊柱侧凸 (AIS) 和非 AIS 对照的骨髓间充质干细胞 (BM-MSC) 的差异基因表达谱、基因本体术语以及京都基因和基因组百科全书通路。背景数据摘要。青少年 AIS 和伴随的全身性骨质减少的发病机制仍不清楚。我们之前的研究表明AIS的BM-MSCs的增殖能力增加，成骨分化能力降低。因此，我们推测MSCs可能在AIS的病因和发病机制中发挥重要作用。方法。在这项研究中，使用微阵列分析来识别 AIS 患者的 BM-MSC 与健康个体的差异表达基因 (DEG)。然后使用全面的生物信息学分析来丰富基因本体和通路的数据集。基于对重要通路中包含的DEGs进行基因信号转导网络分析，筛选出24个潜在的关键基因进行逆转录聚合酶链式反应验证。结果。 AIS 患者的 BM-MSC 中有 1027 个以前未被识别的 DEG。通路分析显示失调的丝裂原激活蛋白激酶（MAPK）信号通路、PI3K-Akt信号通路、钙信号通路、过氧化物酶体增殖物激活受体（PPAR）信号通路、泛素介导的蛋白水解和Notch信号通路，所有这些信号通路在调节MSCs的成骨或成脂分化中发挥重要作用。此外，基因信号转导网络分析表明，丝裂原激活蛋白激酶激酶 1 (MAP2K1)、SMAD 家族成员 3 (SMAD3)、同源框 C6 (HOXC6)、热休克 70kDa 蛋白 6 (HSPA6)、通用转录因子 IIi (GTF2I)、CREB 结合蛋白 (CREBBP)、磷酸肌醇 3 激酶、调节亚基 2 (PIK3R2) 和双特异性磷酸酶 2 (DUSP2) 可能在 AIS 发病机制和伴随的骨质减少中发挥重要作用。结论。该研究首次报道了AIS患者BM-MSCs的差异基因表达谱及相关潜在通路。这些以前未被识别的基因和分子途径可能不仅在 AIS 骨质减少的因果机制中发挥着重要作用，而且在 AIS 的发生和发展中也发挥着重要作用。这些候选基因的鉴定为了解 AIS 的潜在病因学机制提供了新的见解。证据级别：不适用
Study Design. Microarray approach and integrated gene network analysis. Objective. To explore the differential genetic expression profile, gene ontology terms, and Kyoto Encyclopedia of Genes and Genomes pathways in bone marrow mesenchymal stem cells (BM-MSCs) of idiopathic scoliosis (AIS) and non-AIS controls. Summary of Background Data. The pathogenesis of adolescent AIS and the accompanying generalized osteopenia remain unclear. Our previous study suggested increased proliferation ability and decreased osteogenic differentiation ability of BM-MSCs of AIS. Therefore, we hypothesized that MSCs may play a significant role in the etiology and pathogenesis of AIS. Methods. In this study, microarray analysis was used to identify differentially expressed genes (DEGs) of BM-MSCs from AIS patients compared with those from healthy individuals. Comprehensive bioinformatics analyses were then used to enrich datasets for gene ontology and pathway. Based on the gene signal transduction network analysis of DEGs contained in significant pathways, 24 potential crucial genes were selected for validation by reverse transcription polymerase chain reaction. Results. There are 1027 previously unrecognized DEGs in BM-MSCs from AIS patients. Pathway analysis revealed dysregulated mitogen-activated protein kinase (MAPK) signaling pathway, PI3K-Akt signaling pathway, calcium signaling pathway, peroxisome proliferator-activated receptor (PPAR) signaling pathway, ubiquitin-mediated proteolysis, and Notch signaling pathway, all of which have been reported to play an important role in regulating the osteogenic or adipogenic differentiation of MSCs. Furthermore, gene signal transduction networks analysis indicated that mitogen-activated protein kinase kinase 1 (MAP2K1), SMAD family member 3 (SMAD3), homeobox C6 (HOXC6), heat shock 70kDa protein 6 (HSPA6), general transcription factor IIi (GTF2I), CREB binding protein (CREBBP), phosphoinositide-3-kinase, regulatory subunit 2 (PIK3R2), and dual specificity phosphatase 2 (DUSP2) may play essential roles in AIS pathogenesis and accompanied osteopenia. Conclusion. This study reports the differential genes expression profiles of BM-MSCs from AIS patients and related potential pathways for the first time. These previously unrecognized genes and molecular pathways might play a significant role in not only the causal mechanism of osteopenia in AIS, but also the AIS initiation and development. The identification of these candidate genes provides novel insight into the underlying etiological mechanisms of AIS. Level of Evidence: N/A
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DOI：
10.1002/jor.20885
发表时间：
2009-10
期刊：
Journal of orthopaedic research : official publication of the Orthopaedic Research Society
影响因子：
--
作者：
Raggio CL;Giampietro PF;Dobrin S;Zhao C;Dorshorst D;Ghebranious N;Weber JL;Blank RD
通讯作者：
Blank RD
DOI：
10.1083/jcb.153.1.35
发表时间：
2001-04-02
期刊：
The Journal of cell biology
影响因子：
--
作者：
Yang X;Chen L;Xu X;Li C;Huang C;Deng CX
通讯作者：
Deng CX
青少年特发性脊柱侧凸患者骨髓间充质干细胞的差异蛋白质组分析
影响因子：
3.7
作者：
Zhuang Q;Li J;Wu Z;Zhang J;Sun W;Li T;Yan Y;Jiang Y;Zhao RC;Qiu G
通讯作者：
Qiu G
影响因子：
2.8
作者：
Hawasli, Ammar H.;Hullar, Timothy E.;Dorward, Ian G.
通讯作者：
Dorward, Ian G.
影响因子：
9.8
作者：
Fei J;Kaczmarek N;Luch A;Glas A;Carell T;Naegeli H
通讯作者：
Naegeli H