〔Abstract〕 Objective To explore the effect of connective tissue growth factor(CTGF) on aortic calcification and its mechanism. Methods In vitrorat vascular smooth muscle cells(A7 r5) were used for vascular calcification model construction, and the time of calcification was determined using Alizarin staining. The cells were randomly divided into 7 groups to determine the effect of CTGF on calcification. Cells were transfected with CTGF-siRNA plasmid, and the expression of CTGF in cells was detected by RT-PCR and Western blot. To determine the effect of CTGF on cell calcification, cells were randomly divided into 7 groups. Alizarin staining was used to analyze the effect of CTGF on calcification. ELISA was used to detect the alkaline phosphatase(ALP) activity. RT-PCR was used to determine the expression of OPG, RANK and RANKL in A7 r5 cells. Results The optimal time for calcification of A7 r5 was 48 h. The expression of CTGF was reduced in the cells of the CTGF-siRNA group compared to the Control group, indicating that A7 r5 were successfully transfected with the CTGF-siRNA. Compared with the model group, the expression of calcified nodules was reduced, the activity of alkaline phosphatase significantly decreased(P<0.05), and the expression of OPG, RANK and RANKL was also significantly downregulated in the CTGF-siRNA group(P<0.05). Conclusion CTGF-siRNA attenuated A7 r5 cell calcification and alkaline phosphatase activity induced by high phosphorus and calcium, and regulated the OPN/RANK/RANKL signaling pathway, so as to play a therapeutic role in aortic vascular calcification.