Cannabidiol Promotes Osteogenic Differentiation and Modulates Immunomodulatory Properties of hDPSCs
Objectives: Cannabidiol (CBD) has been introduced as an effective analgesia for various chronic conditions such as multiple sclerosis and rheumatoid arthritis. Furthermore, therapeutic potential of CBD has been extensively explored in dentistry. Hence, the present study aimed to investigate the effect of CBD towards the osteogenic differentiation potential and immunosuppressive properties of human dental pulp stem cells (hDPSCs). Methods: hDPSCs were isolated from human dental pulp tissues. The effect of CBD was evaluated in LPS-induced hDPSCs inflammation. The expression of osteogenic-related and immunomodulatory markers was evaluated using quantitative polymerase chain reaction (qPCR). The effects of condition medium following CBD treatment on T cell proliferation were examined using a resazurin assay. Regulatory T cell (Treg) differentiation was investigated using qPCR and flow cytometry analysis. The migration of macrophages was evaluated using transwell migration assay. Results: CBD (1.25 ug/ml) significantly rescued the effect of LPS-induced downregulation of hDPSCs mineralization and osteogenic mRNA expression including COL1A1, BMP2, RUNX2, OSX, DSPP, and DMP1. In addition, CBD significantly abolished the effects of LPS-induced inflammatory and immunomodulatory cytokines, TNFα, IL1β, IL6, TLR2, and TLR4 expression. p38 mitogen-activated protein kinase (p38) inhibitors diminished the effect of CBD-attenuated inflammation in LPS treatment. Further, CBD-derived conditioned media decreased T cell proliferation, promoted Treg differentiation as indicated by FOXP3 mRNA expression, and additionally attenuated migration of macrophages. Conclusions: CBD restored osteogenic differentiation potential of hDPSCs in LPS-induced inflammatory condition. In addition, CBD modulates immunosuppressive properties of hDPSCs through p38 signaling pathway, leading to the inhibition of macrophage migration and T cell proliferation. Moreover, CBD exerts a stimulatory effect on Treg cell differentiation. These results suggest the role of CBD in osteogenic differentiation and immunomodulation in hDPSCs. Therefore, CBD would be a promising bioactive molecule for vital pulp therapy and regenerative endodontics.
2023 South East Asian Division Meeting (Singapore) Singapore
2023 077 Pulp Biology and Regeneration