Objective: To explore the mechanism of circRNA-vgll3 in osteogenic differentiation of human bone marrow mesenchymal stem cells. Methods: BMSCs cells were transfected with circRNA-vgll3, and divided into circRNA-vgll3 high-level group, circRNA-vgll3 low-level group, and negative control group (circRNA-vgll3 not transfected) according to the amount of transfection. The proliferation and apoptosis of BMSCs osteoblasts in each group were analyzed, and the alkaline phosphatase (ALP) activity, type I collagen gray value, bone morphogenetic protein 2 (BMP-2), Runx2 protein, and mRNA expression levels were detected. Results: The circRNA-vgll3 low-level group had a significant inhibitory effect on the proliferation of BMSCs osteoblasts, and the apoptosis rate of the circRNA-vgll3 low-level group was significantly higher than that of the circRNA-vgll3 high-level group ( P < 0.05 ); ALP activity, type I collagen gray value, BMP-2, Runx2 protein, and mRNA expression levels in the high-level circRNA-vgll3 group were significantly higher than those in the low-level circRNA-vgll3 group, and the difference was statistically significant (P < 0.05). Conclusion: Overexpression of circRNA-vgll3 can promote the osteogenic differentiation ability of BMSCs, while low expression of circRNA-vgll3 can inhibit the osteogenic differentiation ability of BMSCs. The main mechanism of action is that circRNA-vgll3 can affect osteogenic differentiation by regulating the Runx2 protein.