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Osteoblast-Secreted Factors Promote Proliferation and Osteogenic Differentiation of Bone Marrow Stromal Cells via VEGF/Heme-Oxygenase-1 Pathway

The hypoxia-inducible factors (HIFα) are the critical factors that couple angiogenesis and osteogenesis by activating transcription of VEGF in osteoblasts. Mice lacking von Hippel–Lindau gene (Vhl), thus overexpressing HIFα in osteoblasts develop extremely dense and highly vascularized long bones. H...

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Autores principales: Zhang, Lian-Fang, Qi, Jin, Zuo, GuiLai, Jia, Peng, Shen, Xing, Shao, Jin, Kang, Hui, Yang, HuiLin, Deng, LianFu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4062480/
https://www.ncbi.nlm.nih.gov/pubmed/24940620
http://dx.doi.org/10.1371/journal.pone.0099946
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author Zhang, Lian-Fang
Qi, Jin
Zuo, GuiLai
Jia, Peng
Shen, Xing
Shao, Jin
Kang, Hui
Yang, HuiLin
Deng, LianFu
author_facet Zhang, Lian-Fang
Qi, Jin
Zuo, GuiLai
Jia, Peng
Shen, Xing
Shao, Jin
Kang, Hui
Yang, HuiLin
Deng, LianFu
author_sort Zhang, Lian-Fang
collection PubMed
description The hypoxia-inducible factors (HIFα) are the critical factors that couple angiogenesis and osteogenesis by activating transcription of VEGF in osteoblasts. Mice lacking von Hippel–Lindau gene (Vhl), thus overexpressing HIFα in osteoblasts develop extremely dense and highly vascularized long bones. Here we provide evidence that osteoblasts lacking Vhl overexpress and secrete high levels of VEGF, which subsequently promotes the proliferation and osteogenic differentiation of bone marrow stromal cells (BMSC) by promoting expression of Heme oxygenase-1 (HO-1) in BMSC. Conditioned medium from osteoblasts Vhl (CM-CRE) promoted the proliferation and osteogenic differentiation of BMSC, in comparison with conditioned medium derived from normal osteoblasts (CM-GFP). Recombinant VEGF stimulated the proliferation and osteogenic differentiation of BMSC culturing in CM-GFP. By contrast, VEGF-neutralizing antibody inhibited the proliferation and osteogenic differentiation of BMSC culturing in CM-CRE. Treatment with a HO-1 inhibitor, SnPP, significantly inhibited VEGF-induced BMSC proliferation and osteogenic differentiation. On the contrary, activation of HO-1 with CoPP reversed the suppressing of VEGF-antibody on the proliferation and osteogesis of BMSC culturing in CM-CRE. These studies suggest that osteoblasts promote the proliferation and osteogenic differentiation of BMCS by VEGF/HO-1 pathway.
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spelling pubmed-40624802014-06-24 Osteoblast-Secreted Factors Promote Proliferation and Osteogenic Differentiation of Bone Marrow Stromal Cells via VEGF/Heme-Oxygenase-1 Pathway Zhang, Lian-Fang Qi, Jin Zuo, GuiLai Jia, Peng Shen, Xing Shao, Jin Kang, Hui Yang, HuiLin Deng, LianFu PLoS One Research Article The hypoxia-inducible factors (HIFα) are the critical factors that couple angiogenesis and osteogenesis by activating transcription of VEGF in osteoblasts. Mice lacking von Hippel–Lindau gene (Vhl), thus overexpressing HIFα in osteoblasts develop extremely dense and highly vascularized long bones. Here we provide evidence that osteoblasts lacking Vhl overexpress and secrete high levels of VEGF, which subsequently promotes the proliferation and osteogenic differentiation of bone marrow stromal cells (BMSC) by promoting expression of Heme oxygenase-1 (HO-1) in BMSC. Conditioned medium from osteoblasts Vhl (CM-CRE) promoted the proliferation and osteogenic differentiation of BMSC, in comparison with conditioned medium derived from normal osteoblasts (CM-GFP). Recombinant VEGF stimulated the proliferation and osteogenic differentiation of BMSC culturing in CM-GFP. By contrast, VEGF-neutralizing antibody inhibited the proliferation and osteogenic differentiation of BMSC culturing in CM-CRE. Treatment with a HO-1 inhibitor, SnPP, significantly inhibited VEGF-induced BMSC proliferation and osteogenic differentiation. On the contrary, activation of HO-1 with CoPP reversed the suppressing of VEGF-antibody on the proliferation and osteogesis of BMSC culturing in CM-CRE. These studies suggest that osteoblasts promote the proliferation and osteogenic differentiation of BMCS by VEGF/HO-1 pathway. Public Library of Science 2014-06-18 /pmc/articles/PMC4062480/ /pubmed/24940620 http://dx.doi.org/10.1371/journal.pone.0099946 Text en © 2014 Zhang et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Zhang, Lian-Fang
Qi, Jin
Zuo, GuiLai
Jia, Peng
Shen, Xing
Shao, Jin
Kang, Hui
Yang, HuiLin
Deng, LianFu
Osteoblast-Secreted Factors Promote Proliferation and Osteogenic Differentiation of Bone Marrow Stromal Cells via VEGF/Heme-Oxygenase-1 Pathway
title Osteoblast-Secreted Factors Promote Proliferation and Osteogenic Differentiation of Bone Marrow Stromal Cells via VEGF/Heme-Oxygenase-1 Pathway
title_full Osteoblast-Secreted Factors Promote Proliferation and Osteogenic Differentiation of Bone Marrow Stromal Cells via VEGF/Heme-Oxygenase-1 Pathway
title_fullStr Osteoblast-Secreted Factors Promote Proliferation and Osteogenic Differentiation of Bone Marrow Stromal Cells via VEGF/Heme-Oxygenase-1 Pathway
title_full_unstemmed Osteoblast-Secreted Factors Promote Proliferation and Osteogenic Differentiation of Bone Marrow Stromal Cells via VEGF/Heme-Oxygenase-1 Pathway
title_short Osteoblast-Secreted Factors Promote Proliferation and Osteogenic Differentiation of Bone Marrow Stromal Cells via VEGF/Heme-Oxygenase-1 Pathway
title_sort osteoblast-secreted factors promote proliferation and osteogenic differentiation of bone marrow stromal cells via vegf/heme-oxygenase-1 pathway
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4062480/
https://www.ncbi.nlm.nih.gov/pubmed/24940620
http://dx.doi.org/10.1371/journal.pone.0099946
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