Osteocyte-induced angiogenesis via VEGF–MAPK-dependent pathways in endothelial cells

Prasadam, Indira, Zhou, Yinghong, Du, Zhibin, Chen, Jiezhong, Crawford, Ross, & Xiao, Yin (2014) Osteocyte-induced angiogenesis via VEGF–MAPK-dependent pathways in endothelial cells. Molecular and Cellular Biochemistry, 386(1-2), pp. 15-25.

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Recently, it has been suggested osteocytes control the activities of bone formation (osteoblasts) and resorption (osteoclast), indicating their important regulatory role in bone remodelling. However, to date, the role of osteocytes in controlling bone vascularisation remains unknown. Our aim was to investigate the interaction between endothelial cells and osteocytes and to explore the possible molecular mechanisms during angiogenesis. To model osteocyte/endothelial cell interactions, we co-cultured osteocyte cell line (MLOY4) with endothelial cell line (HUVECs). Co-cultures were performed in 1:1 mixture of osteocytes and endothelial cells or by using the conditioned media (CM) transfer method. Real-time cell migration of HUVECs was measured with the transwell migration assay and xCELLigence system. Expression levels of angiogenesis- related genes were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The effect of vascular endothelial growth factor (VEGF) and mitogen-activated phosphorylated kinase (MAPK) signaling were monitored by western blotting using relevant antibodies and inhibitors. During the bone formation, it was noted that osteocyte dendritic processes were closely connected to the blood vessels. The CM generated from MLOY4 cells-activated proliferation, migration, tube-like structure formation, and upregulation of angiogenic genes in endothelial cells suggesting that secretory factor(s) from osteocytes could be responsible for angiogenesis. Furthermore, we identified that VEGF secreted from MLOY4-activated VEGFR2–MAPK–ERK-signaling pathways in HUVECs. Inhibiting VEGF and/or MAPK–ERK pathways abrogated osteocyte-mediated angiogenesis in HUVEC cells. Our data suggest an important role of osteocytes in regulating angiogenesis.

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8 citations in Web of Science®

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ID Code: 63979
Item Type: Journal Article
Refereed: Yes
Keywords: Osteocyte, Endothelial cells, Bone, Angiogenesis, Co-culture
DOI: 10.1007/s11010-013-1840-2
ISSN: 0300-8177
Subjects: Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000)
Divisions: Current > Institutes > Institute of Health and Biomedical Innovation
Current > QUT Faculties and Divisions > Science & Engineering Faculty
Deposited On: 09 Jan 2014 04:22
Last Modified: 25 Feb 2014 05:11

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