VCAM-1 and GFPT-2: Predictive markers of osteoblast differentiation in human dental pulp stem cells
VCAM-1 and GFPT-2: Predictive markers of osteoblast differentiation in human dental pulp stem cells
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DOI：
10.1016/j.bone.2022.116575
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发表时间：
2022-10-14
期刊：
影响因子：
4.1
通讯作者：
Chikazu, Daichi
中科院分区：
文献类型：
--
作者：
Hatori, Ayano;Fujii, Yasuyuki;Chikazu, Daichi
牙髓干细胞是间充质干细胞中具有高度增殖和多向分化潜能的细胞。然而，一些研究表明，DPSCs的成骨分化潜能存在个体差异，而决定这些差异的因素尚不清楚。目的：鉴定影响DPSCs成骨分化潜能个体差异的基因。用ALP和von Kossa染色将DPSCs分为成骨分化能力高和低的两组（HG或LG），用RNA-seq比较基因表达谱。结果：RNA-seq图谱显示，HG中VCAM 1和GFPT 2的表达水平明显高于LG，siRNA分析结果显示，VCAM 1和GFPT 2的敲除显著降低了成骨标志物的表达。此外，我们分析了这两个基因参与DPSC分化的细胞信号传导。结论：高表达VCAM 1和GFPT 2的DPSCs具有较高的成骨分化能力，VCAM 1介导的Ras-MEK-Erk和PI 3 K/ Akt信号通路参与了DPSCs的成骨分化，GFPT 2介导的HBP信号通路影响了DPSCs的成骨分化。评估未分化DPSC中VCAM 1和GFPT 2的表达可能预测使用DPSC的骨再生治疗的结果。此外，DPSC中VCAM 1和GFPT 2的表达水平可能有助于为骨再生的同种异体细胞移植选择供体。
Introduction: Dental pulp stem cells (DPSCs) have high proliferative and multilineage differentiation potential in mesenchymal stem cells. However, several studies have indicated that there are individual differences in the potential for osteogenic differentiation of DPSCs, and the factors determining these differences are unknown.Objective: To identify the genes responsible for the individual differences in the osteogenic differentiation ability of DPSCs.Methods: We divided DPSCs into high and low osteogenic differentiation ability groups (HG or LG) with ALP and von Kossa stain, and compared the gene expression patterns using RNA-seq. In addition, genes that may affect osteogenic differentiation were knocked down using small interfering RNA (siRNA) and their effects were investigated.Results: The RNA-seq patterns revealed that VCAM1 and GFPT2 were significantly expressed at higher levels in the HG than in the LG. The results of siRNA analysis showed that VCAM1 and GFPT2 knockdown significantly reduced the expression of osteogenic markers. Furthermore, we analyzed the involvement of these two genes in cell signaling in DPSC differentiation. The results indicated that the VCAM1-mediated Ras-MEK-Erk and PI3K/ Akt pathways are involved in the osteogenic differentiation of DPSCs, and that GFPT2-mediated HBP signaling influences the osteogenic differentiation of DPSCs.Conclusions: These findings indicate that DPSCs that highly express VCAM1 and GFPT2 have a high capacity for osteogenic differentiation. Evaluation of VCAM1 and GFPT2 expression in undifferentiated DPSCs may predict the outcome of bone regenerative therapy using DPSCs. Moreover, the expression levels of VCAM1 and GFPT2 in DPSCs may be useful in setting criteria for selecting donors for allogeneic cell transplantation for bone regeneration.