title: Elevated PTH induces endothelial-to-chondrogenic transition in aortic endothelial cells.
abstract: Previous studies have shown that increased parathyroid hormone (PTH) attributable to secondary hyperparathyroidism in chronic kidney disease accelerates the arteriosclerotic fibrosis and calcification. Although the underlying mechanisms remain largely unknown, endothelial cells (ECs) have recently been demonstrated to participate in calcification in part by providing chondrogenic cells via the endothelial-to-mesenchymal transition (EndMT). Therefore, this study aimed to investigate whether elevated PTH could induce endothelial-to-chondrogenic transition in aortic ECs and to determine the possible underlying signaling pathway. We found that treatment of ECs with PTH significantly upregulated the expression of EndMT-related markers. Accordingly, ECs treated with PTH exhibited chondrogenic potential. In vivo, lineage-tracing model-subjected mice with endothelial-specific green fluorescent protein fluorescence to chronic PTH infusion showed a marked increase in the aortic expression of chondrocyte markers, and confocal microscopy revealed the endothelial origin of cells expressing chondrocyte markers in the aorta after PTH infusion. Furthermore, this in vitro study showed that PTH enhanced the nuclear localization of β-catenin in ECs, whereas β-catenin siRNA or DKK1, an inhibitor of β-catenin nuclear translocation, attenuated the upregulation of EndMT-associated and chondrogenic markers induced by PTH. In summary, our study demonstrated that elevated PTH could induce the transition of ECs to chondrogenic cells via EndMT, possibly mediated by the nuclear translocation of β-catenin.
authors: Institute of Nephrology, Zhongda Hospital, Southeast University School of Medicine, Nanjing, China; and.
authors: Min
authors: M
authors: Wu
authors: Institute of Nephrology, Zhongda Hospital, Southeast University School of Medicine, Nanjing, China; and.|Division of Nephrology, Department of Medicine, Duke University Medical Center and Durham VA Medical Center, Durham, North Carolina.
authors: Jian-Dong
authors: JD
authors: Zhang
authors: Institute of Nephrology, Zhongda Hospital, Southeast University School of Medicine, Nanjing, China; and.
authors: Ri-Ning
authors: RN
authors: Tang
authors: Division of Nephrology, Department of Medicine, Duke University Medical Center and Durham VA Medical Center, Durham, North Carolina.
authors: Steven D
authors: SD
authors: Crowley
authors: Institute of Nephrology, Zhongda Hospital, Southeast University School of Medicine, Nanjing, China; and.
authors: Hong
authors: H
authors: Liu
authors: Institute of Nephrology, Zhongda Hospital, Southeast University School of Medicine, Nanjing, China; and.
authors: Lin-Li
authors: LL
authors: Lv
authors: Institute of Nephrology, Zhongda Hospital, Southeast University School of Medicine, Nanjing, China; and.
authors: Kun-Ling
authors: KL
authors: Ma
authors: Institute of Nephrology, Zhongda Hospital, Southeast University School of Medicine, Nanjing, China; and liubc64@163.com.
authors: Bi-Cheng
authors: BC
authors: Liu
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects*; D019070:Cell Lineage; D002478:Cells, Cultured; D020219:Chondrogenesis / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D006801:Humans; D008822:Mice, Transgenic; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010641:Phenotype; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: C495270:CTNNB1 protein, human; C470125:PTH protein, human; D010281:Parathyroid Hormone; D051176:beta Catenin
keywords: chondrogenic transition; endothelial cells; parathyroid hormone; β-catenin