| First Author | Yao J | Year | 2021 |
| Journal | JCI Insight | Volume | 6 |
| Issue | 10 | PubMed ID | 33848269 |
| Mgi Jnum | J:316116 | Mgi Id | MGI:6751038 |
| Doi | 10.1172/jci.insight.143023 | Citation | Yao J, et al. (2021) Shifting osteogenesis in vascular calcification. JCI Insight 6(10) |
| abstractText | Transitions between cell fates commonly occur in development and disease. However, reversing an unwanted cell transition in order to treat disease remains an unexplored area. Here, we report a successful process of guiding ill-fated transitions toward normalization in vascular calcification. Vascular calcification is a severe complication that increases the all-cause mortality of cardiovascular disease but lacks medical therapy. The vascular endothelium is a contributor of osteoprogenitor cells to vascular calcification through endothelial-mesenchymal transitions, in which endothelial cells (ECs) gain plasticity and the ability to differentiate into osteoblast-like cells. We created a high-throughput screening and identified SB216763, an inhibitor of glycogen synthase kinase 3 (GSK3), as an inducer of osteoblastic-endothelial transition. We demonstrated that SB216763 limited osteogenic differentiation in ECs at an early stage of vascular calcification. Lineage tracing showed that SB216763 redirected osteoblast-like cells to the endothelial lineage and reduced late-stage calcification. We also found that deletion of GSK3beta in osteoblasts recapitulated osteoblastic-endothelial transition and reduced vascular calcification. Overall, inhibition of GSK3beta promoted the transition of cells with osteoblastic characteristics to endothelial differentiation, thereby ameliorating vascular calcification. |
