RANKL is a downstream mediator for insulin-induced osteoblastic differentiation of vascular smooth muscle cells.
Several reports have shown that circulating insulin level is positively correlated with arterial calcification; however, the relationship between insulin and arterial calcification remains controversial and the mechanism involved is still unclear. We used calcifying vascular smooth muscle cells (CVS...
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doaj-fb77e21e60bf43b9b4714f23bc0be8172020-11-24T21:26:37ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-01612e2903710.1371/journal.pone.0029037RANKL is a downstream mediator for insulin-induced osteoblastic differentiation of vascular smooth muscle cells.Ling-Qing YuanJia-Hua ZhuHua-Wen WangQiu-Hua LiangHui XieXian-Ping WuHua ZhouRong-Rong CuiZhi-Feng ShengHou-De ZhouXiao ZhuGuan-Ying LiuYou-Shuo LiuEr-Yuan LiaoSeveral reports have shown that circulating insulin level is positively correlated with arterial calcification; however, the relationship between insulin and arterial calcification remains controversial and the mechanism involved is still unclear. We used calcifying vascular smooth muscle cells (CVSMCs), a specific subpopulation of vascular smooth muscle cells that could spontaneously express osteoblastic phenotype genes and form calcification nodules, to investigate the effect of insulin on osteoblastic differentiation of CVSMCs and the cell signals involved. Our experiments demonstrated that insulin could promote alkaline phosphatase (ALP) activity, osteocalcin expression and the formation of mineralized nodules in CVSMCs. Suppression of receptor activator of nuclear factor κB ligand (RANKL) with small interfering RNA (siRNA) abolished the insulin-induced ALP activity. Insulin induced the activation of extracellular signal-regulated kinase (ERK)1/2, mitogen-activated protein kinase (MAPK) and RAC-alpha serine/threonine-protein kinase (Akt). Furthermore, pretreatment of human osteoblasts with the ERK1/2 inhibitor PD98059, but not the phosphoinositide 3-kinase (PI3K) inhibitor, LY294002, or the Akt inhibitor, 1L-6-hydroxymethyl-chiro-inositol 2-(R)-2-O-methyl-3-O-octadecylcarbonate (HIMO), abolished the insulin-induced RANKL secretion and blocked the promoting effect of insulin on ALP activities of CVSMCs. Recombinant RANKL protein recovered the ALP activities decreased by RANKL siRNA in insulin-stimulated CVSMCs. These data demonstrated that insulin could promote osteoblastic differentiation of CVSMCs by increased RANKL expression through ERK1/2 activation, but not PI3K/Akt activation.http://europepmc.org/articles/PMC3240644?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ling-Qing Yuan Jia-Hua Zhu Hua-Wen Wang Qiu-Hua Liang Hui Xie Xian-Ping Wu Hua Zhou Rong-Rong Cui Zhi-Feng Sheng Hou-De Zhou Xiao Zhu Guan-Ying Liu You-Shuo Liu Er-Yuan Liao |
spellingShingle |
Ling-Qing Yuan Jia-Hua Zhu Hua-Wen Wang Qiu-Hua Liang Hui Xie Xian-Ping Wu Hua Zhou Rong-Rong Cui Zhi-Feng Sheng Hou-De Zhou Xiao Zhu Guan-Ying Liu You-Shuo Liu Er-Yuan Liao RANKL is a downstream mediator for insulin-induced osteoblastic differentiation of vascular smooth muscle cells. PLoS ONE |
author_facet |
Ling-Qing Yuan Jia-Hua Zhu Hua-Wen Wang Qiu-Hua Liang Hui Xie Xian-Ping Wu Hua Zhou Rong-Rong Cui Zhi-Feng Sheng Hou-De Zhou Xiao Zhu Guan-Ying Liu You-Shuo Liu Er-Yuan Liao |
author_sort |
Ling-Qing Yuan |
title |
RANKL is a downstream mediator for insulin-induced osteoblastic differentiation of vascular smooth muscle cells. |
title_short |
RANKL is a downstream mediator for insulin-induced osteoblastic differentiation of vascular smooth muscle cells. |
title_full |
RANKL is a downstream mediator for insulin-induced osteoblastic differentiation of vascular smooth muscle cells. |
title_fullStr |
RANKL is a downstream mediator for insulin-induced osteoblastic differentiation of vascular smooth muscle cells. |
title_full_unstemmed |
RANKL is a downstream mediator for insulin-induced osteoblastic differentiation of vascular smooth muscle cells. |
title_sort |
rankl is a downstream mediator for insulin-induced osteoblastic differentiation of vascular smooth muscle cells. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2011-01-01 |
description |
Several reports have shown that circulating insulin level is positively correlated with arterial calcification; however, the relationship between insulin and arterial calcification remains controversial and the mechanism involved is still unclear. We used calcifying vascular smooth muscle cells (CVSMCs), a specific subpopulation of vascular smooth muscle cells that could spontaneously express osteoblastic phenotype genes and form calcification nodules, to investigate the effect of insulin on osteoblastic differentiation of CVSMCs and the cell signals involved. Our experiments demonstrated that insulin could promote alkaline phosphatase (ALP) activity, osteocalcin expression and the formation of mineralized nodules in CVSMCs. Suppression of receptor activator of nuclear factor κB ligand (RANKL) with small interfering RNA (siRNA) abolished the insulin-induced ALP activity. Insulin induced the activation of extracellular signal-regulated kinase (ERK)1/2, mitogen-activated protein kinase (MAPK) and RAC-alpha serine/threonine-protein kinase (Akt). Furthermore, pretreatment of human osteoblasts with the ERK1/2 inhibitor PD98059, but not the phosphoinositide 3-kinase (PI3K) inhibitor, LY294002, or the Akt inhibitor, 1L-6-hydroxymethyl-chiro-inositol 2-(R)-2-O-methyl-3-O-octadecylcarbonate (HIMO), abolished the insulin-induced RANKL secretion and blocked the promoting effect of insulin on ALP activities of CVSMCs. Recombinant RANKL protein recovered the ALP activities decreased by RANKL siRNA in insulin-stimulated CVSMCs. These data demonstrated that insulin could promote osteoblastic differentiation of CVSMCs by increased RANKL expression through ERK1/2 activation, but not PI3K/Akt activation. |
url |
http://europepmc.org/articles/PMC3240644?pdf=render |
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