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Isolation of Mesenchymal Stem Cells from Human Alveolar Periosteum and Effects of Vitamin D on Osteogenic Activity of Periosteum-derived Cells
Published on: May 4, 2018
In vitro assessment of the osteotoxic potential of diuron in human BMSCs
Yiwei Xie1, Zixuan Chen2, Xiaohui Wu3
1Department of Orthopedics, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China; Shanghai Key Laboratory of Flexible Medical Robotics, Tongren Hospital, Institute of Medical Robotics, Shanghai Jiao Tong University, Shanghai 200336, China; Center for Spinal Minimally Invasive Research, Shanghai Jiao Tong University, Shanghai, 200336, China.
Abstract:
Osteoporosis (OP) is an age-related chronic skeletal disorder that has been increasingly linked to environmental chemical stressors. Diuron, a widely used substituted phenylurea herbicide with high environmental persistence, has been extensively characterized for multi-organ toxicity; however, its potential impact on bone homeostasis remains insufficiently characterized. In this study, we combined network toxicology, molecular docking, and in vitro experiments to conduct an initial hazard-identification assessment of the osteotoxic potential of diuron and to explore candidate mechanisms. Network analysis identified 73 overlapping targets between diuron and OP, with EGFR, NFKB1, STAT1, PARP1, and PTGS2 as hub genes. Functional enrichment analysis suggested that calcium signaling and PI3K/Akt signaling may be involved. Analysis of the GSE230665 dataset provided exploratory supportive evidence that several predicted targets were differentially expressed in an OP-related disease context. Molecular docking further provided supportive in silico evidence for potential interactions between diuron and the predicted hub proteins, while experimental target engagement remains to be established. In vitro, diuron reduced the viability of bone marrow mesenchymal stem cells (BMSCs) in a dose-dependent manner and impaired osteogenic differentiation, as indicated by decreased ALP and ARS staining and downregulation of osteogenic marker genes. Diuron exposure was also associated with increased expression of the predicted hub genes in BMSCs. Western blot analysis demonstrated that diuron reduced the phosphorylation levels of PI3K and Akt, whereas treatment with the PI3K activator 740 YP partially restored pathway activity. Collectively, these results suggest that diuron exposure may compromise BMSC osteogenic potential under in vitro conditions, with PI3K/Akt suppression as a plausible contributing mechanism. These findings reveal a preliminary osteotoxic signal and warrant follow-up studies in vivo and in human-relevant models to evaluate real-world relevance.
