Chondrogenic differentiation of rat bone marrow mesenchymal stem cells induced by puerarin and tetrandrine

Objective:This study aims to clarify the effect of the active components puerarin and tetrandrine on the chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs).Methods:Using network pharmacology, protein targets of puerarin and tetrandrine were predicted, and a database of cartilage formation targets was established. The protein target information related to disease was then collected, and the drug-targeting network was constructed by analyzing the protein-protein interactions. Genes related to chondrogenesis induced by puerarin and tetrandrine and chondroblast differentiation signaling pathways were searched. Finally, potential drug- and disease-related genes, as well as proteins, were screened and verified using real-time RT-PCR and western blotting.Results:Network pharmacological studies have shown that puerarin and tetrandrine are involved in BMSCs cartilage differentiation. The experimental results showed that puerarin and tetrandrine could regulate the expression of cartilage differentiation-related genes and proteins. Puerarin increased the protein expression of COL2A1, COL10A1, MMP13, and SOX-9, as well as the gene expression of Col2a1, Mmp13, Tgfb1, and Sox-9. Tetrandrine increased the protein expression of COL2A1, COL10A1, MMP13, and SOX-9, as well as the gene expression of Col10a1, Tgfb1, Sox-9, and Acan. The combination of puerarin and tetrandrine increased the protein expression of COL2A1, COL10A1, MMP13, and SOX-9 and the gene expression of Col2a1, Col10a1, Sox-9, and Acan.Conclusions:Puerarin, tetrandrine, and their combination can promote the proliferation of BMSCs and induce their differentiation into chondrocytes, and they are thus expected to be inducers of chondrogenic differentiation. These results suggest that puerarin and tetrandrine have potential therapeutic effects on osteoarthritis.