Nonthermal biocompatible plasma in stimulating osteogenic differentiation by targeting p38/ FOXO1 and PI3K/AKT pathways in hBMSCs

Osteoporosis is manifested by decreased bone density and deterioration of bone architecture, increasing the risk of bone fractures Human bone marrow mesenchymal stem cells (hBMSCs)-based tissue engineering serves as a crucial technique for regenerating lost bone and preventing osteoporosis. Non-thermal biocompatible plasma (NBP) is a potential new therapeutic approach employed in several biomedical applications, including regenerative medicine. NBP affects bone remodeling; however, its role in the regulation of osteogenic differentiation in hBMSCs remains largely unexplored. This study aimed to explore the efficiency of NBP in promoting osteogenic differentiation, and the molecular pathways through which these responses occurred in hBMSCs. We found that NBP facilitated osteogenic differentiation through the upregulation of the bone morphogenic protein signal (BMPs) cascade, which in turn induced the expression of p38 and inhibited the forkhead box protein O1 (FOXO1). To further gain insight into the mechanism through which NBP extensively triggers the initiation of osteogenic differentiation in hBMSCs, PI3K/AKT pathway was also analyzed. Overall, these results highlight that NBP enhances osteogenic differentiation in hBMSCs by the stimulation of the p38/FOXO1 through PI3K/AKT signaling pathways. Therefore, the application of NBP in hBMSCs may offer tremendous therapeutic prospects in the treatment of bone regeneration and osteoporosis prevention.