Choi Yong Jun, Song Insun, Jin Yilan, Jin Hyun-Seok, Ji Hyung Min, Jeong Seon-Yong, Won Ye-Yeon, Chung Yoon-Sok
Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, South Korea.
School of Biological Sciences, Seoul National University, Seoul, South Korea.
Gene. 2017 Oct 20;632:7-15. doi: 10.1016/j.gene.2017.08.015. Epub 2017 Aug 24.
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.
基因改变是骨质疏松症发生发展的主要促成因素。成骨细胞和脂肪细胞有着共同的起源，即间充质干细胞（MSCs），它们的基因决定因素可能在骨质疏松症与肥胖症的关系中具有重要意义。在本研究中，我们旨在利用人MSCs分离骨质疏松症患者与正常对照中的差异表达基因（DEGs），并阐明与骨质疏松症和脂肪生成相关的共同途径和基因。人MSCs取自绝经后女性在骨科手术中股骨的骨髓。使用下一代测序（NGS）技术进行RNA测序（RNA-seq）。利用RNA-seq数据鉴定DEGs。运用 Ingenuity 通路分析（IPA）来阐明与骨质疏松症和脂肪生成相关的共同途径。使用逆转录聚合酶链反应（RT-PCR）分析，在其他独立的骨质疏松症和肥胖受试者中验证共同途径的候选基因。在绝经后骨质疏松症患者与正常骨密度（BMD）对照之间鉴定出53个DEGs。大多数基因变化与细胞分化有关。核受体亚家族4 A组（NR4A）家族被确定为可能与成骨和脂肪生成相关的共同基因。骨质疏松症患者中NR4A1的mRNA表达水平显著高于对照组（p = 0.018）。肥胖患者中NR4A2的mRNA表达水平显著高于对照组（p = 0.041）。MSCs中的一些基因变化参与了骨质疏松症的病理生理过程。NR4A家族可能包含与骨质疏松症和肥胖症相关的共同基因。
