Elevated PTH induces endothelial-to-chondrogenic transition in aortic endothelial cells.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Wu, M; Zhang, J-D; Tang, R-N; Crowley, SD; Liu, H; Lv, L-L; Ma, K-L; Liu, B-C

Published Date

  • March 1, 2017

Published In

Volume / Issue

  • 312 / 3

Start / End Page

  • F436 - F444

PubMed ID

  • 27582099

Pubmed Central ID

  • 27582099

Electronic International Standard Serial Number (EISSN)

  • 1522-1466

Digital Object Identifier (DOI)

  • 10.1152/ajprenal.00210.2016

Language

  • eng

Conference Location

  • United States