Objective In previous work, our research team developed a bone-targeting drug delivery system for the total flavonoids of rhizoma drynariae (Aln-gel-BMSN-TFRD). This study aimed to explore the effects and mechanisms of Aln-gel-BMSN-TFRD on the proliferation, apoptosis, and osteogenic differentiation of MC3T3-E1 cells, providing potential new methods for the clinical treatment of osteoporosis (OP). Methods The impact of Aln-gel-BMSN-TFRD on cell viability was assessed using the CCK-8 assay to determine the optimal concentration. Flow cytometry was used to evaluate its effect on cell apoptosis. Alizarin Red and alkaline phosphatase staining were employed to observe its influence on osteogenic differentiation. The expression levels of Runx2, Osx, BMP2, Wnt1, Wnt3a, and β-catenin were measured using qPCR and Western blot. Results Compared to TFRD, Aln-gel-BMSN-TFRD significantly enhanced cell proliferation, inhibited apoptosis, promoted osteogenic differentiation, and upregulated the expression of Runx2, Osx, BMP2, Wnt1, Wnt3a, and β-catenin. Conclusion Aln-gel-BMSN- TFRD is superior to TFRD in protecting cells, promoting osteogenic differentiation, upregulating the expression of osteogenic related factors, and activating Wnt/β-catenin pathway. It has the potential to be used as a new treatment for OP. |