State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.
Department of Oral Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.
Bioengineered. 2022 Mar;13(3):6880-6894. doi: 10.1080/21655979.2022.2044274.
Human umbilical cord mesenchymal stem cells (hUCMSCs) are attractive therapeutic cells for tissue engineering to treat bone defects. However, how the cells can differentiate into bone remains unclear. Long non-coding RNAs (lncRNAs) are non-coding RNAs that participate in many biological processes, including stem cell differentiation. In this study, we investigated the profiles and functions of lncRNAs in the osteogenic differentiation of hUCMSCs. We identified 343 lncRNAs differentially expressed during osteogenic differentiation, of which 115 were upregulated and 228 were downregulated. We further analyzed these lncRNAs using bioinformatic analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. GO and KEGG pathway analysis showed that 'intracellular part' and 'Phosphatidylinositol signaling system' were the most correlated molecular function and pathway, respectively. We selected the top 10 upregulated lncRNAs to construct six competing endogenous RNA networks. We validated the impact of the lncRNA H19 on osteogenic differentiation by overexpressing it in hUCMSCs. Overall, our results pave the way to detailed studies of the molecular mechanisms of hUCMSC osteogenic differentiation, and they provide a new theoretical basis to guide the therapeutic application of hUCMSCs.
人脐带间充质干细胞（hUCMSCs）是组织工程治疗骨缺损的有吸引力的治疗细胞。然而，细胞如何分化为骨仍然不清楚。长非编码 RNA（lncRNA）是参与许多生物学过程的非编码 RNA，包括干细胞分化。在这项研究中，我们研究了 lncRNA 在 hUCMSC 成骨分化中的谱和功能。我们鉴定了在成骨分化过程中差异表达的 343 个 lncRNA，其中 115 个上调，228 个下调。我们进一步使用生物信息学分析，包括基因本体论（GO）和京都基因与基因组百科全书（KEGG）途径分析，对这些 lncRNA 进行了分析。GO 和 KEGG 途径分析表明，“细胞内部分”和“磷脂酰肌醇信号系统”分别是最相关的分子功能和途径。我们选择了前 10 个上调的 lncRNA 来构建六个竞争内源 RNA 网络。我们通过在 hUCMSCs 中转染高表达 h19lncRNA 来验证 lncRNA H19 对成骨分化的影响。总的来说，我们的结果为详细研究 hUCMSC 成骨分化的分子机制铺平了道路，并为指导 hUCMSC 的治疗应用提供了新的理论基础。
