Effects of alendronate on the Notch1-RBP-Jκ signaling pathway in the osteogenic differentiation and mineralization of vascular smooth muscle cells

Abstract

Cardiovascular disease and osteoporosis are major causes of mortality in the elderly. Alendronate, a bisphosphonate, is widely used in the treatment of osteoporosis and may be used to inhibit vascular calcification. However, its mechanisms are not completely understood. The present study aimed to explore novel signaling mechanisms behind the action of alendronate in the osteoblastic differentiation of rat aortic vascular smooth muscle cells (VSMCs). The osteoblastic differentiation of VSMCs was induced by an osteogenic medium. Using von Kossa staining and direct cellular calcium content determination, mineralization was found to be significantly increased in VSMCs induced with osteogenic medium, consistent with an enhanced alkaline phosphatase activity. Osteoblastic differentiation in VSMCs was significantly reduced by the action of alendronate in a dose-dependent manner. In addition, the expression of Notch1 and RBP-Jκ was significantly upregulated in VSMCs cultured with osteogenic medium at the mRNA and protein levels. The effects of Notch1-RBP-Jκ were inhibited by treatment with alendronate in a dose-dependent manner. In summary, results of the current study indicate that alendronate inhibits vascular calcification through downregulation of the Notch1-RBP-Jκ signaling pathway.