{"doi":"10.1172/jci.insight.143023","title":"Shifting osteogenesis in vascular calcification","abstract":"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 GSK3β in osteoblasts recapitulated osteoblastic-endothelial transition and reduced vascular calcification. Overall, inhibition of GSK3β promoted the transition of cells with osteoblastic characteristics to endothelial differentiation, thereby ameliorating vascular calcification.","journal":"JCI Insight","year":2021,"id":161269,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":27,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9557,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":389718,"name":"Xiuju Wu","orcid":null,"position":1,"is_corresponding":false},{"id":389716,"name":"Xiaojing Qiao","orcid":null,"position":2,"is_corresponding":false},{"id":388999,"name":"Daoqin Zhang","orcid":"0000-0002-7694-8119","position":3,"is_corresponding":false},{"id":291057,"name":"Li Zhang","orcid":"0000-0002-9386-8938","position":4,"is_corresponding":false},{"id":526797,"name":"A. Jocelyn","orcid":"0000-0002-3259-2333","position":5,"is_corresponding":false},{"id":526798,"name":"Xinjiang Cai","orcid":"0000-0001-8933-7133","position":6,"is_corresponding":false},{"id":385046,"name":"Kristina I. Boström","orcid":"0000-0002-7745-5025","position":7,"is_corresponding":false},{"id":389001,"name":"Yucheng Yao","orcid":"0000-0003-0483-9180","position":8,"is_corresponding":false},{"id":388997,"name":"Jiayi Yao","orcid":"0000-0001-9235-2406","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":null,"created_at":"2026-07-18T23:44:52.299342Z","pmid":"33848269","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}