IADR Abstract Archives
Aspirin Induces Osteogenic Differentiation of Dental Pulp Stem Cells
Objectives: The objectives of this study were to investigate the utility of drug reposition approach using connectivity-mapping to identify compounds that could potentially induce osteogenic differentiation of dental pulp stem cells (DPSCs) and to validate their effects by in-vitro testing.
Methods: Connectivity mapping was carried out using the programme sscMap and publicly-available datasets to create initially an osteogenic gene signature for DPSCs and then identify compounds that could modify the gene signature to potentially induce osteogenic differentiation of DPSCs. One compound with a significant positive connection score was then selected. Compound toxicity was tested by 3-day, 5-day and 7-day MTT assays. Expression of the osteogenic genes, RUNX2, ALPL, COL1A1 and DSPP was assessed at 24h, 7 days and 14 days by qPCR. Calcification at day 14 and 21 was assessed by Alizarin Red staining assay.
Results: Gene expression analysis using sscMap revealed novel osteogenic gene signature for DPSCs undergoing osteogenic differentiation. Mapping thin gene signature to compounds library identified aspirin as a potential osteogenic candidate with significant positive connection score. MTT assays showed a lack of toxicity for aspirin at concentrations of 0.5mM and 0.05mM at all time points. Osteogenic genes, RUNX2, COL1A1, DSPP and ALPL were upregulated in DPSCs treated with 0.05mM aspirin in comparison to negative controls. Increased calcification at 14 and 21 days were also evident in aspirin-treated cells compared to negative controls.
Conclusions: This study shows that aspirin increases expression of osteogenic genes and induces calcification and ALPL activity in DPSCs. Therefore, aspirin may be a viable alternative for inducing osteogenic differentiation of DPSCs in-vitro and a potential pulp capping material in-vivo. Furthermore, the results suggest that connectivity-mapping may be a valid approach for identifying compounds that can induce stem cell differentiation.
Methods: Connectivity mapping was carried out using the programme sscMap and publicly-available datasets to create initially an osteogenic gene signature for DPSCs and then identify compounds that could modify the gene signature to potentially induce osteogenic differentiation of DPSCs. One compound with a significant positive connection score was then selected. Compound toxicity was tested by 3-day, 5-day and 7-day MTT assays. Expression of the osteogenic genes, RUNX2, ALPL, COL1A1 and DSPP was assessed at 24h, 7 days and 14 days by qPCR. Calcification at day 14 and 21 was assessed by Alizarin Red staining assay.
Results: Gene expression analysis using sscMap revealed novel osteogenic gene signature for DPSCs undergoing osteogenic differentiation. Mapping thin gene signature to compounds library identified aspirin as a potential osteogenic candidate with significant positive connection score. MTT assays showed a lack of toxicity for aspirin at concentrations of 0.5mM and 0.05mM at all time points. Osteogenic genes, RUNX2, COL1A1, DSPP and ALPL were upregulated in DPSCs treated with 0.05mM aspirin in comparison to negative controls. Increased calcification at 14 and 21 days were also evident in aspirin-treated cells compared to negative controls.
Conclusions: This study shows that aspirin increases expression of osteogenic genes and induces calcification and ALPL activity in DPSCs. Therefore, aspirin may be a viable alternative for inducing osteogenic differentiation of DPSCs in-vitro and a potential pulp capping material in-vivo. Furthermore, the results suggest that connectivity-mapping may be a valid approach for identifying compounds that can induce stem cell differentiation.