An in vivo genome wide gene expression study of circulating monocytes suggested GBP1, STAT1 and CXCL10 as novel risk genes for the differentiation of peak bone mass
An in vivo genome wide gene expression study of circulating monocytes suggested GBP1, STAT1 and CXCL10 as novel risk genes for the differentiation of peak bone mass
复制标题
循环单核细胞的体内全基因组基因表达研究表明 GBP1、STAT1 和 CXCL10 是峰值骨量分化的新风险基因
DOI：
10.1016/j.bone.2008.05.016
复制
发表时间：
2009-05-01
期刊：
影响因子：
4.1
通讯作者：
Deng, Hong-Wen
中科院分区：
文献类型：
--
作者：
Lei, Shu-Feng;Wu, Shan;Deng, Hong-Wen
峰值骨量（PBM）是骨质疏松症的重要决定因素。循环单核细胞作为破骨细胞的早期祖细胞，产生骨代谢的重要分子。为了寻找对PBM变异具有重要功能的基因，我们对具有极低（N = 12）与高（N = 14）PBM的人绝经前受试者的循环单核细胞进行了全基因组基因差异表达研究。我们使用了AffytechnologyHG-U133 plus 2. 0 GeneChip（R）阵列。我们鉴定了70个差异表达探针组（p < 0.01），对应于49个独特基因。校正假发现率后，有3个基因（STAT 1，信号转导和转录激活因子1; GBPI，鸟苷酸结合蛋白1：CXCL 10;趋化因子（C-X-C基序）配体101）的表达差异显著（p < 0.05）。RT-PCR结果独立证实了GBPI基因的显著差异表达，以及STAT 1的差异表达趋势。功能分析表明，这三个基因与破骨细胞的增殖、迁移、分化、迁移、趋化、粘附等过程有关。因此，我们可以初步假设，这三个基因可能有助于差异破骨细胞，这可能最终导致差异PBM。我们的研究结果表明，GBPI，STAT 1和CXCL 10可能是PBM在单核细胞阶段分化的新的风险基因。(C)2008年由Elsevier Inc.出版
Peak bone mass (PBM) is an important determinant of osteoporosis. Circulating monocytes serve as early progenitors of osteoclasts and produce important molecules for bone metabolism. To search for genes functionally important for PBM variation, we performed a whole genome gene differential expression study of circulating monocytes in human premenopausal subjects with extremely low (N = 12) vs. high (N = 14) PBM. We used Affymetrix HG-U133 plus2.0 GeneChip (R) arrays. We identified 70 differential expression probe sets (p < 0.01) corresponding to 49 unique genes. After false discovery rate adjustment, three genes [STAT1, signal transducer and activator of transcription 1; GBPI, guanylate binding protein 1: CXCL10, Chemokine (C-X-C motif) ligand 101 expressed significantly differentially (p < 0.05). The RT-PCR results independently confirmed the significantly differential expression of GBPI gene, and the differential expression trend of STAT1. Functional analyses suggested that the three genes are associated with the osteoclastogenic processes of proliferation, migration, differentiation, migration, chemotaxis, adhesion. Therefore, we may tentatively hypothesize that the three genes may potentially contribute to differential osteoclastogenesis, which may in the end lead to differential PBM. Our results indicate that the GBPI, STAT1 and CXCL10 may be novel risk genes for the differentiation of PBM at the monocyte stage. (C) 2008 Published by Elsevier Inc.