Li Li, Wang Xue Qing, Liu Xiao Ting, Guo Rui, Zhang Rui Dong
College of Life Sciences, Inner Mongolia Normal University, Hohhot, Inner Mongolia 010022, China.
Hefei Laboratory Center, Ping An Healthcare Investment Management Co, Ltd.
Math Biosci Eng. 2019 Jun 27;16(5):5947-5971. doi: 10.3934/mbe.2019298.
Osteoporosis is the most common bone metabolic disease. Abnormal osteoclast formation and resorption play a fundamental role in osteoporosis pathogenesis. Recent researches have greatly broaden our understanding of molecular mechanisms of osteoporosis. However, the molecular mechanisms of key mRNAs and lncRNAs, and their interactions leading to osteoporosis are still not entirely clear. The purpose of this work is to study the key mRNAs and lncRNAs, and their interactions involved in bone mineral homeostasis and osteoclastogenesis. Systematic analyses such as differential expression analysis, GO and KEGG analysis, and PPI network construction revealed that up-regulated mRNAs were significantly enriched in inflammation-related pathways. Moreover, we observed that the down-regulated proteins, including JDP2, HADC4, HDAC5, CDYL2, ACADVL, ACSL1 and BRD4, were key components in the down-regulated PPI network, indicating that the downregulation of histone deacetylases and cofactors, such as, HDAC4, HDAC5 and JDP2 may be critical regulators in osteoclastogenesis. In addition, we also highlighted one lncRNA, RP11-498C9.17, was highly correlated with epigenetic regulators, such as HDAC4, MORF4L1, HMGA1 and DND1, indicating that the lncRNA RP11-498C9.17 may also be an epigenetic regulator. In conclusion, our integrative analysis reveals key mRNAs and lncRNAs, involved in bone mineral homeostasis and osteoclastogenesis, which not only broaden our insights into lncRNAs in bone mineral homeostasis and osteoclastogenesis, but also improve our understanding of molecular mechanism.
骨质疏松症是最常见的骨代谢疾病。破骨细胞形成和吸收异常在骨质疏松症发病机制中起关键作用。最近的研究极大地拓宽了我们对骨质疏松症分子机制的理解。然而,关键mRNA和lncRNA的分子机制及其导致骨质疏松症的相互作用仍不完全清楚。这项工作的目的是研究参与骨矿物质稳态和破骨细胞生成的关键mRNA和lncRNA及其相互作用。差异表达分析、GO和KEGG分析以及PPI网络构建等系统分析表明,上调的mRNA在炎症相关途径中显著富集。此外,我们观察到下调的蛋白质,包括JDP2、HADC4、HDAC5、CDYL2、ACADVL、ACSL1和BRD4,是下调的PPI网络中的关键成分,表明组蛋白去乙酰化酶及其辅因子如HDAC4、HDAC5和JDP2的下调可能是破骨细胞生成的关键调节因子。此外,我们还强调了一个lncRNA,RP11-498C9.17,与表观遗传调节因子如HDAC4、MORF4L1、HMGA1和DND1高度相关,表明lncRNA RP11-498C9.17也可能是一种表观遗传调节因子。总之,我们的综合分析揭示了参与骨矿物质稳态和破骨细胞生成的关键mRNA和lncRNA,这不仅拓宽了我们对骨矿物质稳态和破骨细胞生成中lncRNA的认识,也提高了我们对分子机制的理解。