Transcriptional profiling of human femoral mesenchymal stem cells in osteoporosis and its association with adipogenesis
Transcriptional profiling of human femoral mesenchymal stem cells in osteoporosis and its association with adipogenesis
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DOI：
10.1016/j.gene.2017.08.015
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发表时间：
2017-10-20
期刊：
影响因子：
3.5
通讯作者：
Chung, Yoon-Sok
中科院分区：
文献类型：
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作者：
Choi, Yong Jun;Song, Insun;Chung, Yoon-Sok
遗传改变是骨质疏松症发生的主要因素。本研究旨在利用人骨髓间充质干细胞（MSCs）分离骨质疏松症患者和正常人的差异表达基因（DEG），阐明骨质疏松症和脂肪形成的共同途径和基因。人MSC从骨科手术期间绝经后妇女的股骨骨髓中获得。使用下一代测序（NGS）技术进行RNA测序（RNA-seq）。使用RNA-seq数据鉴定DEG。采用抗骨质疏松途径分析（IPA）来阐明与骨质疏松和脂肪生成相关的共同途径。采用RT-PCR（逆转录-聚合酶链反应）技术，在绝经后骨质疏松症患者和正常骨密度（BMD）对照者中，对共同途径的候选基因进行了验证。大多数遗传变化与细胞分化有关。核受体亚家族4 A组（NR 4A）家族被鉴定为可能与成骨和脂肪形成相关的共同基因。NR 4A 1 mRNA的表达水平在骨质疏松症患者中显著高于对照组（p = 0.018）。NR 4A 2 mRNA的表达水平在肥胖患者中显著高于对照组（p = 0.041）。骨髓间充质干细胞中的一些遗传变化参与了骨质疏松症的病理生理过程。NR 4A家族可能包含与骨质疏松和肥胖相关的共同基因。
Genetic alterations are major contributing factors in the development of osteoporosis. Osteoblasts and adipocytes share a common origin, mesenchymal stem cells (MSCs), and their genetic determinants might be important in the relationship between osteoporosis and obesity.In the present study, we aimed to isolate differentially expressed genes (DEGs) in osteoporosis and normal controls using human MSCs, and elucidate the common pathways and genes related to osteoporosis and adipogenesis. Human MSCs were obtained from the bone marrow of femurs from postmenopausal women during orthopedic surgeries. RNA sequencing (RNA-seq) was carried out using next-generation sequencing (NGS) technology. DEGs were identified using RNA-seq data. Ingenuity pathway analysis (IPA) was used to elucidate the common pathway related to osteoporosis and adipogenesis. Candidate genes for the common pathway were validated with other independent osteoporosis and obese subjects using RT-PCR (reverse transcription-polymerase chain reaction) analysis.Fifty-three DEGs were identified between postmenopausal osteoporosis patients and normal bone mineral density (BMD) controls. Most of the genetic changes were related to the differentiation of cells. The nuclear receptor subfamily 4 group A (NR4A) family was identified as possible common genes related to osteogenesis and adipogenesis. The expression level of the mRNA of NR4A1 was significantly higher in osteoporosis patients than in controls (p = 0.018). The expression level of the mRNA of NR4A2 was significantly higher in obese patients than in controls (p = 0.041). Some genetic changes in MSCs are involved in the pathophysiology of osteoporosis. The NR4A family might comprise common genes related to osteoporosis and obesity.