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Arterial calcification is a complex and active regulated process, which results from a process of osteoblastic differentiation of vascular smooth muscle cells (VSMCs). Leptin, the product of the ob gene, mainly regulates food intake and energy expenditure and recently has been considered to be correlated with the arterial calcification. However, the mechanisms of the effects of leptin on osteoblastic differentiation of VSMCs are unknown. We used calcifying vascular smooth muscle cells (CVSMCs) as a model to investigate the relationship between leptin and the osteoblastic differentiation of CVSMCs and the signaling pathways involved. Our experiments demonstrated that leptin could increase expression of receptor activator of nuclear factor-κB ligand (RANKL) and bone morphogenetic protein 4 (BMP4), as well as alkaline phosphatase (ALP) activity, runt-related transcription factor 2 expression, calcium deposition …