The process of vascular calcification shares numerous similarities with that of skeletal mineralization and involves the deposition of hydroxyapatite crystals in arteries and cardiac valves. However, the underlying cellular mechanism remains to be fully elucidated. Microarray analysis in the present study demonstrated that greater than 2,000 genes were upregulated during the calcification of murine vascular smooth muscle cells (VSMCs), of which osterix (OSX) and integrin‑binding sialoprotein (IBSP) were the most significantly differentially expressed genes. Following the validation of increased OSX and IBSP expression by reverse transcription‑quantitative polymerase chain reaction in calcifying murine VSMCs induced by aldosterone. Subsequent to transfection with siRNA‑OSX, results indicated that OSX may inhibit calcification of VSMCs via IBSP. It was suggested that the increased OSX expression in calcifying VSMCs may reflect the well‑established prenatal role of OSX. A full understanding of the importance of OSX in this pathological process would improve understanding of the pathogenesis of vascular calcification.