Systems genetics and bioinformatics analyses using ESR1-correlated genes identify potential candidates underlying female bone development.
Systems genetics and bioinformatics analyses using ESR1-correlated genes identify potential candidates underlying female bone development.
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DOI：
10.1016/j.ygeno.2023.110769
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发表时间：
2024-01
期刊：
影响因子：
4.4
通讯作者：
Lu, Lu
中科院分区：
文献类型：
--
作者：
Bajpai, Akhilesh K.;Gu, Qingqing;Jiao, Yan;Starlard-Davenport, Athena;Gu, Weikuan;Quarles, Leigh Darryl;Xiao, Zhousheng;Lu, Lu
雌激素受体α (ESR1)参与E2信号传导并在绝经后骨质流失中起重要作用。然而，ESR1背后的分子网络尚未被探索。我们使用系统遗传学和生物信息学来鉴定绝经后骨质流失中与Esr1相关的重要基因。我们在女性BXD股骨中鉴定了约2300个esr1共表达基因，功能分析显示“成骨细胞信号”是最富集的途径。PPI网络鉴定出25个“女性候选骨”。遗传调控分析显示RUNX2是一个关键的TF。ANKRD1和RUNX2在骨质疏松症患者和健康对照组之间存在显著差异。Sp7、Col1a1和Pth1r与BXD小鼠多种股骨表型相关。miR-3121-3p靶向Csf1、Ankrd1、Sp7和Runx2。β-雌二醇处理可显著提高小鼠成骨细胞中这些候选蛋白的表达。我们的研究发现esr1相关基因Ankrd1、Runx2、Csf1和Sp7可能在女性骨骼发育中发挥重要作用。
Estrogen receptor α (ESR1) is involved in E2 signaling and plays a major role in postmenopausal bone loss. However, the molecular network underlying ESR1 has not been explored. We used systems genetics and bioinformatics to identify important genes associated with Esr1 in postmenopausal bone loss. We identified ~2300 Esr1-coexpressed genes in female BXD bone femur, functional analysis of which revealed ‘osteoblast signaling’ as the most enriched pathway. PPI network led to the identification of 25 ‘female bone candidates’. The generegulatory analysis revealed RUNX2 as a key TF. ANKRD1 and RUNX2 were significantly different between osteoporosis patients and healthy controls. Sp7, Col1a1 and Pth1r correlated with multiple femur bone phenotypes in BXD mice. miR-3121–3p targeted Csf1, Ankrd1, Sp7 and Runx2. β-estradiol treatment markedly increased the expression of these candidates in mouse osteoblast. Our study revealed that Esr1-correlated genes Ankrd1, Runx2, Csf1 and Sp7 may play important roles in female bone development.
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影响因子：
3.7
作者：
Eguchi T;Watanabe K;Hara ES;Ono M;Kuboki T;Calderwood SK
通讯作者：
Calderwood SK
影响因子：
4
作者：
Cooper, C.;Cole, Z. A.;Holroyd, C. R.;Earl, S. C.;Harvey, N. C.;Dennison, E. M.;Melton, L. J.;Cummings, S. R.;Kanis, J. A.
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3.7
作者：
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通讯作者：
Jakob F
DOI：
10.1073/pnas.0906947106
发表时间：
2009-09-15
影响因子：
11.1
作者：
Castellano, Leandro;Giamas, Georgios;Stebbing, Justin
通讯作者：
Stebbing, Justin