Dong Qiannan, Zhang Hengwei, Zhang Qian, Fei Xiuzhi, Ruan Jianping, He Longlong
Key laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiao Tong University, Xi'an 710000, China.
Center of Oral Public Health, College of Stomatology,Xi'an, Jiaotong 710000, China.
Tissue Cell. 2025 Oct;96:103012. doi: 10.1016/j.tice.2025.103012. Epub 2025 Jun 10.
Dental pulp mesenchymal stem cells (DPSCs) are typically cultivated in vitro under normoxic conditions, which may adversely affect their biological functions during research and treatment. Dimethyloxalylglycine (DMOG) is a small-molecule drug that has demonstrated impressive therapeutic outcomes in conditions such as osteoporosis.
However, the influence of DMOG on the osteogenesis associated with DPSCs remains inadequately understood. We propose that DMOG may significantly impact the biological functions related to osteogenesis in DPSCs when exposed to normoxic conditions.
DPSCs were obtained through tissue block enzyme digestion. Tube formation experiment was conducted, quantitative polymerase chain reaction (qPCR) was employed to assess the angiogenic activity of DPSCs. Additionally, alkaline phosphatase (ALP) activity tests, alizarin red staining (ARS), qPCR and western blotting (WB) assays were utilized to evaluate the osteogenic activity of DPSCs. The proposed mechanism was confirmed through repeated experiments.
DMOG significantly influences the osteogenic functions of DPSCs under normoxic conditions. Our findings further confirm that DMOG stimulates the phosphatidylinositol 3-kinase (PI3K)/Protein kinase B (AKT) signaling pathway in DPSCs via phosphorylation. Inhibition of this pathway can partially impede the biological effects of DPSCs related to osteogenesis and angiogenesis.
We have addressed the gap in understanding the effect of DMOG on the osteogenesis of DPSCs. Unlike previous studies that examined the regulation of osteogenesis in stem cells by DMOG, our findings suggest that a lower dose of DMOG is sufficient to enhance the osteogenesis of DPSCs. This could represent a promising strategy for cellular therapy in bone regeneration.
牙髓间充质干细胞（DPSCs）通常在常氧条件下进行体外培养，这在研究和治疗过程中可能会对其生物学功能产生不利影响。二甲基乙二酰甘氨酸（DMOG）是一种小分子药物，已在骨质疏松症等病症中显示出令人瞩目的治疗效果。
然而，DMOG对与DPSCs相关的成骨作用的影响仍未得到充分了解。我们提出，当暴露于常氧条件时，DMOG可能会显著影响DPSCs中与成骨相关的生物学功能。
通过组织块酶消化法获取DPSCs。进行管形成实验，采用定量聚合酶链反应（qPCR）评估DPSCs的血管生成活性。此外，利用碱性磷酸酶（ALP）活性测试、茜素红染色（ARS）、qPCR和蛋白质印迹（WB）分析来评估DPSCs的成骨活性。通过重复实验证实了所提出的机制。
DMOG在常氧条件下显著影响DPSCs的成骨功能。我们的研究结果进一步证实，DMOG通过磷酸化刺激DPSCs中的磷脂酰肌醇3激酶（PI3K）/蛋白激酶B（AKT）信号通路。抑制该通路可部分阻碍DPSCs与成骨和血管生成相关的生物学效应。
我们填补了对DMOG对DPSCs成骨作用影响理解上的空白。与之前研究DMOG对干细胞成骨调节作用的研究不同，我们的研究结果表明，较低剂量的DMOG就足以增强DPSCs的成骨作用。这可能代表了一种在骨再生细胞治疗中很有前景的策略。
