Title | Bisphosphonates induce the osteogenic gene expression in co-cultured human endothelial and mesenchymal stem cells |
Publication Type | Papers in Scientific Journals |
Year of Publication | 2013 |
Authors | Ribeiro V. P., Garcia M., Oliveira R., Gomes P. S., Colaço B., and Fernandes M. H. |
Abstract | Bisphosphonates (BPs) are known to affect bone homeostasis and also to have anti-angiogenic properties. Because of the intimate relationship between angiogenesis and osteogenesis, this study analysed the effects of Alendronate (AL) and Zoledronate (ZL) in the expression of endothelial and osteogenic genes on interacting endothelial and mesenchymal stem cells, an issue that was not previously addressed. Alendronate and ZL, 10 12–106 M, were evaluated in a direct co-culture system of human dermal microvascular endothelial cells (HDMEC) and human bone marrow mesenchymal stem cells (HMSC), over a period of 14 days. Experiments with the respective monocultures were run in parallel. Alendronate and ZL caused an initial dose-dependent stimulation in the cell proliferation in the monocultures and co-cultures, and did not interfere with their cellular organization. In HDMEC monocultures, the expression of the endothelial genes CD31, VE-cadherin and VEGFR2 was downregulated by AL and ZL. In HMSC monocultures, the BPs inhibited VEGF expression, but up-regulated the expression of the osteogenic genes alkaline phosphatase (ALP), bone morphogenic protein-2 (BMP-2) and osteocalcin (OC) and, to a greater extent, osteoprotegerin (OPG), a negative regulator of the osteoclastic differentiation, and increased ALP activity. In co-cultured HDMEC/HMSC, AL and ZL decreased the expression |
Journal | Journal of Cellular and Molecular Medicine |
Date Published | 2013-10-31 |
Publisher | John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine |
DOI | 10.1111/jcmm.12154 |
URL | http://onlinelibrary.wiley.com/advanced/search/results |
Keywords | co-cultured cells, human dermal microvascular endothelial cells (HDMEC), osteogenic gene expression, human mesenchymal stem cells (HMSC), Alendronate, endothelial gene expression, Zoledronate |
Rights | openAccess |
Peer reviewed | yes |
Status | published |