Jia Linglu, Zhang Yunpeng, Li Dongfang, Zhang Wenjing, Zhang Dongjiao, Xu Xin
Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, China.
Department of Oral Implantology, The Affiliated Stomatology Hospital of Kunming Medical University, Kunming, China.
J Cell Mol Med. 2021 May 24;25(13):6217-31. doi: 10.1111/jcmm.16571.
Both human periodontal ligament stem cells (hPDLSCs) and human gingival mesenchymal stem cells (hGMSCs) are candidate seed cells for bone tissue engineering, but the osteo-differentiation ability of the latter is weaker than the former, and the mechanisms are unknown. To explore the potential regulation of mRNAs and long non-coding RNAs (lncRNAs), this study obtained the gene expression profiles of hPDLSCs and hGMSCs in both undifferentiated and osteo-differentiated conditions by microarray assay and then analysed the common and specific differentially expressed mRNAs and lncRNAs in hPDLSCs and hGMSCs through bioinformatics method. The results showed that 275 mRNAs and 126 lncRNAs displayed similar changing patterns in hPDLSCs and hGMSCs after osteogenic induction, which may regulate the osteo-differentiation in both types of cells. In addition, the expression of 223 mRNAs and 238 lncRNAs altered only in hPDLSCs after osteogenic induction, and 177 mRNAs and 170 lncRNAs changed only in hGMSCs. These cell-specific differentially expressed mRNAs and lncRNAs could underlie the different osteo-differentiation potentials of hPDLSCs and hGMSCs. Finally, dickkopf Wnt signalling pathway inhibitor 1 (DKK1) was proved to be one regulator for the weaker osteo-differentiation ability of hGMSCs through validation experiments. We hope these results help to reveal new mRNAs-lncRNAs-based molecular mechanism for osteo-differentiation of hPDLSCs and hGMSCs and provide clues on strategies for improving stem cell-mediated bone regeneration.
人牙周膜干细胞（hPDLSCs）和人牙龈间充质干细胞（hGMSCs）都是骨组织工程的候选种子细胞，但后者的成骨分化能力弱于前者，其机制尚不清楚。为了探索mRNA和长链非编码RNA（lncRNAs）的潜在调控作用，本研究通过微阵列分析获得了未分化和经成骨分化条件下hPDLSCs和hGMSCs的基因表达谱，然后通过生物信息学方法分析了hPDLSCs和hGMSCs中共同的和特异性的差异表达mRNA和lncRNAs。结果显示，275个mRNA和126个lncRNAs在成骨诱导后的hPDLSCs和hGMSCs中呈现相似的变化模式，它们可能调控这两种细胞的成骨分化。此外，223个mRNA和238个lncRNAs的表达仅在成骨诱导后的hPDLSCs中发生改变，177个mRNA和170个lncRNAs仅在hGMSCs中发生变化。这些细胞特异性差异表达的mRNA和lncRNAs可能是hPDLSCs和hGMSCs不同成骨分化潜能的基础。最后，通过验证实验证明Dickkopf Wnt信号通路抑制剂1（DKK1）是hGMSCs成骨分化能力较弱的一个调节因子。我们希望这些结果有助于揭示基于mRNA-lncRNAs的hPDLSCs和hGMSCs成骨分化新分子机制，并为改善干细胞介导的骨再生策略提供线索。
