Featured as ectopic mineralization along blood vessels, vascular calcification is a major risk factor for a number of prevalent diseases including atherosclerosis. As recent studies identify vascular calcification as a tightly regulated process recapitulating embryonic bone formation, in this study, RNA-seq data generated from rabbit models with inherited or induced hyperlipidemia and atherosclerosis were used, to investigate bone formation related signals and biological processes in atherosclerotic vascular calcification. Evident activation of bone formation was found, together with presence and functioning of bone resorption cell osteoclasts, which were found to possibly also promote bone formation in this disease. Resistance of bone formation and calcification were also found, through down-regulation of pro ossification regulators and up-regulation of protective inhibitors and Wnt antagonists. Levels of activation and resistance of bone formation differed between the two disease models, suggesting different underlying mechanisms and corresponding treatments. In addition, loss-of-function of protective inhibitors KL and SOST, and possibly crucial role of GPNMB were also highlighted for treatment or further study. (C) 2018 Elsevier Inc. All rights reserved.