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Human vascular cell responses to the circulating bone hormone osteocalcin
Author(s) -
Millar Sophie A.,
Anderson Susan I.,
O'sullivan Saoirse E.
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.28707
Subject(s) - osteocalcin , angiogenesis , endocrinology , medicine , protein kinase b , mapk/erk pathway , cell growth , phosphorylation , microbiology and biotechnology , endothelial stem cell , chemistry , creb , vascular smooth muscle , biology , in vitro , biochemistry , alkaline phosphatase , transcription factor , smooth muscle , gene , enzyme
The purpose of this study was to characterize the direct effects of uncarboxylated osteocalcin (ucOCN) on vascular cell biology in vitro, to assess its potential function in pathophysiological conditions such as atherosclerosis. Human aortic endothelial cells (HAECs) and smooth muscle cells (HASMCs) were treated with ucOCN (0.1–50 ng/ml) and changes in phosphorylation of intracellular signaling proteins, angiogenesis, proliferation, migration, monolayer permeability, and protein secretion were measured. In HAECs, phosphorylated JNK and CREB were decreased with ucOCN ( p < 0.05). In HASMCs, phosphorylated p70S6K and NF‐ΚB were increased by ucOCN ( p < 0.05). Cell proliferation increased in both cell types dose dependently which was blocked by AKT and ERK pathway inhibitors. ucOCN did not affect cell permeability, angiogenesis, or migration. The direct activity of ucOCN on vascular cells is recognized, particularly its proliferative effects. However, at least in physiological settings, it does not appear that osteocalcin may directly promote atherogenesis based on the outcomes measured.