Toor Salman M, Wani Sachin, Albagha Omar M E
College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar.
Rheumatology and Bone Disease Unit, Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom.
Front Genet. 2021 Nov 15;12:781272. doi: 10.3389/fgene.2021.781272. eCollection 2021.
Osteoclasts are the sole bone resorbing cells, which undertake opposing roles to osteoblasts to affect skeletal mass and structure. However, unraveling the comprehensive molecular mechanisms behind osteoclast differentiation is necessitated to overcome limitations and scarcity of available data, particularly in relation with the emerging roles of long non-coding RNAs (LncRNAs) in gene expression. In this study, we performed comprehensive and progressive analyses of the dynamic transcriptomes of murine osteoclasts, generated . We compared the total RNA-based transcriptomes of murine bone marrow derived cells with differentiated osteoclasts, while focusing on potentially novel genes and LncRNAs, to uncover critical genes and their associated pathways, which are differentially regulated during osteoclast differentiation. We found 4,214 differentially regulated genes during osteoclast differentiation, which included various types of LncRNAs. Among the upregulated protein coding genes not previously associated with osteoclast are , , and , while downregulated genes included , , and . Notably, we report as a novel gene related to osteoclast activity since knockout mice exhibit increased bone mineral density. Moreover, the differentially expressed LncRNAs included antisense and long intergenic non-coding RNAs, among others. Overall, immune-related and metabolism-related genes were downregulated, while anatomical morphogenesis and remodeling-related genes were upregulated in early-differentiated osteoclasts with sustained downregulation of immune-related genes in mature osteoclasts. The gene signatures and the comprehensive transcriptome of osteoclast differentiation provided herein can serve as an invaluable resource for deciphering gene dysregulation in osteoclast-related pathologic conditions.
破骨细胞是唯一负责骨吸收的细胞，其作用与成骨细胞相反，会影响骨骼质量和结构。然而，有必要深入了解破骨细胞分化背后的全面分子机制，以克服现有数据的局限性和稀缺性，特别是考虑到长链非编码RNA（LncRNAs）在基因表达中的新作用。在本研究中，我们对小鼠破骨细胞的动态转录组进行了全面且递进的分析。我们比较了小鼠骨髓来源细胞与分化破骨细胞基于总RNA的转录组，同时关注潜在的新基因和LncRNAs，以揭示在破骨细胞分化过程中差异调节的关键基因及其相关途径。我们发现破骨细胞分化过程中有4214个差异调节基因，其中包括各种类型的LncRNAs。在先前与破骨细胞无关的上调蛋白质编码基因中，有[具体基因1]、[具体基因2]、[具体基因3]和[具体基因4]，而下调基因包括[具体基因5]、[具体基因6]、[具体基因7]和[具体基因8]。值得注意的是，我们报告[具体基因]是一个与破骨细胞活性相关的新基因，因为该基因敲除小鼠表现出骨矿物质密度增加。此外，差异表达的LncRNAs包括反义RNA和长链基因间非编码RNA等。总体而言，在早期分化的破骨细胞中，免疫相关和代谢相关基因下调，而解剖形态发生和重塑相关基因上调，在成熟破骨细胞中免疫相关基因持续下调。本文提供的破骨细胞分化的基因特征和全面转录组可作为解读破骨细胞相关病理状况中基因失调的宝贵资源。
