Gu Huijie, Huang Zhongyue, Zhou Kaifeng, Chen Guangnan, Bian Chong, Xu Jun, Yin Xiaofan
Department of Orthopedics, Minhang Hospital, Fudan University, Shanghai, China.
Front Cell Dev Biol. 2021 Sep 30;9:719851. doi: 10.3389/fcell.2021.719851. eCollection 2021.
Osteoporosis (OP) has the characteristics of a systematically impaired bone mass, strength, and microstructure. Long non-coding RNAs (lncRNAs) are longer than 200 nt, and their functions in osteoporosis is yet not completely understood. We first harvested the bone marrow mesenchymal stem cells (BMSCs) from ovariectomy (OVX) and sham mice. Then, we systematically analyzed the differential expressions of lncRNAs and messenger RNAs (mRNAs) and constructed lncRNA-mRNA coexpression network in order to identify the function of lncRNA in osteoporosis. Totally, we screened 743 lncRNAs (461 upregulated lncRNAs and 282 downregulated lncRNAs) and 240 mRNAs (128 upregulated and 112 downregulated) with significantly differential expressions in OP compared to normal. We conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional analyses to investigate the functions and pathways of the differential expression of messenger RNAs (mRNAs), a coexpressed network of lncRNA/mRNA. Quantitative PCR (qPCR) validated that the expressions of NONMMUT096150.1, NONMMUT083450.1, and NONMMUT029743.2 were all downregulated, whereas NONMMUT026970.2, NONMMUT051734.2, NONMMUT003617.2, and NONMMUT034049.2 were all upregulated in the OVX group. NONMMUT096150.1, as a key lncRNA in OP, was identified to modulate the adipogenesis of BMSCs. Further analysis suggested that NONMMUT096150.1 might modulate the adipogenesis of BMSCs via the peroxisome proliferator-activated receptor (PPAR) signaling pathway, AMPK signaling pathway, and the lipolysis regulation in adipocyte and adipocytokine signaling pathway. Our study expands the understanding of lncRNA in the pathogenesis of OP.
骨质疏松症(OP)具有骨量、骨强度和骨微结构系统性受损的特征。长链非编码RNA(lncRNAs)长度超过200个核苷酸,其在骨质疏松症中的功能尚未完全明确。我们首先从去卵巢(OVX)小鼠和假手术小鼠中分离出骨髓间充质干细胞(BMSCs)。然后,我们系统地分析了lncRNAs和信使核糖核酸(mRNAs)的差异表达,并构建了lncRNA-mRNA共表达网络,以确定lncRNA在骨质疏松症中的作用。与正常情况相比,我们总共筛选出743个lncRNAs(461个上调lncRNAs和282个下调lncRNAs)和240个mRNAs(128个上调和112个下调)在OP中具有显著差异表达。我们进行了基因本体论(GO)和京都基因与基因组百科全书(KEGG)功能分析,以研究信使核糖核酸(mRNAs)差异表达的功能和途径,即lncRNA/mRNA共表达网络。定量聚合酶链反应(qPCR)验证了NONMMUT096150.1、NONMMUT083450.1和NONMMUT029743.2在OVX组中的表达均下调,而NONMMUT026970.2、NONMMUT051734.2、NONMMUT003617.2和NONMMUT034049.2在OVX组中的表达均上调。NONMMUT096150.1作为OP中的关键lncRNA,被确定可调节BMSCs的脂肪生成。进一步分析表明,NONMMUT096150.1可能通过过氧化物酶体增殖物激活受体(PPAR)信号通路、AMPK信号通路以及脂肪细胞中的脂解调节和脂肪细胞因子信号通路来调节BMSCs的脂肪生成。我们的研究扩展了对lncRNA在OP发病机制中的理解。