Network pharmacology of rhizoma drynariae exosomes: a novel approach to bone regeneration.

This study delves into the osteogenic properties of Rhizoma Drynariae, a traditional Chinese medicinal herb known for facilitating bone repair. Rhizoma Drynariae-derived exosomes were isolated and investigated to understand their impact on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). The exosomes significantly enhanced differentiation by elevating the expression of osteogenic genes such as RUNX2, OPN, and OCN, and promoting calcium nodule formation. Network pharmacology and bioinformatics analysis identified 86 pivotal genes, pinpointing the critical role of the TNF signaling pathway and inflammatory response in this enhancement. Functional validation showed that TNF signaling inhibition reduced osteogenic gene expression, mineralization, and ALP activity, confirming its essential role. These findings reveal the intricate molecular interactions underpinning the effects of Rhizoma Drynariae exosomes, providing a foundation for developing innovative therapeutic strategies to treat bone disorders and regenerate damaged bone tissue effectively. Graphical Abstract. Experimental Validation and Potential Molecular Mechanisms of Rhizoma Drynariae -Exosomes in Promoting Osteogenic Differentiation of BMSCs. GRAPHICAL ABSTRACT: Experimental Validation and Potential Molecular Mechanisms of Rhizoma Drynariae -Exosomes in Promoting Osteogenic Differentiation of BMSCs. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10616-025-00860-1.