Abstract
Introduction
Arterial calcification is a major factor for cardiovascular events and is characterized by vascular smooth muscle cells (VSMCs) transformed into osteoblast-like cells. Long non-coding RNAs (lncRNA) were recognized as important regulators of diverse biological processes. Previous studies have demonstrated that lncRNAs could regulate the proliferation and apoptosis of VSMCs. LncRNA-ANCR (Anti-differentiation ncRNA) is an essential mediator governing the differentiation of human osteoblast. However, it is unclear whether ANCR could regulate the osteoblastic differentiation of VSMCs. In this study, we determined the effect of ANCR on VSMCs differentiation and arterial calcification.
Materials and Methods
Both cellular and mouse model of arterial calcification were, respectively, established to investigate the role of ANCR in the mechanism of arterial calcification. ANCR overexpressing lentivirus were used to investigate the effects of ANCR on the expression of bone proteins and autophagy-related molecules.
Results
ANCR could inhibit β-glycerophosphate (β-GP)-induced VSMCs osteoblastic differentiation and mineralization due to decreased expressions of Runt-related transcription factor 2, bone morphogenetic protein-2, and formation of mineralized nodule, and attenuate high calcitriol-induced mice model of arterial calcification. Furthermore, ANCR could significantly increase LC3 and autophagy protein 5 expression in β-GP-stimulated VSMCs, and the effect could be inhibited by 3-methyladenine, a pharmacological inhibitor of autophagy.
Conclusion
ANCR may inhibit the osteoblastic differentiation of VSMCs and attenuate mice arterial calcification through activating autophagy.
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Acknowledgements
This work was supported by the National Natural Science Foundation of China (81400860), Natural Science Foundation of Shandong Province (ZR2019MH087 and ZR2017LH024), Projects of Medical and Health Technology Development Program in Shandong Province (2016WS0168).
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Zhang, X., Chen, J., Meng, Q. et al. The protective effects of long non-coding RNA-ANCR on arterial calcification. J Bone Miner Metab 38, 421–431 (2020). https://doi.org/10.1007/s00774-019-01076-y
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DOI: https://doi.org/10.1007/s00774-019-01076-y