The effect of bisphosphonates on the endothelial differentiation of mesenchymal stem cells

Sharma, Dileep, Hamlet, Stephen Mark, Petcu, Eugen Bogdan, and Ivanovski, Saso (2016) The effect of bisphosphonates on the endothelial differentiation of mesenchymal stem cells. Scientific Reports, 6. 20580. pp. 1-11.

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The contribution of the local stem cell niche to providing an adequate vascular framework during healing cannot be overemphasized. Bisphosphonates (BPs) are known to have a direct effect on the local vasculature, but their effect on progenitor cell differentiation is unknown. This in vitro study evaluated the effect(s) of various BPs on the differentiation of human placental mesenchymal stem cells (pMSCs) along the endothelial lineage and their subsequent functional and morphogenic capabilities. pMSC multipotency was confirmed by successful differentiation into cells of both the osteogenic and endothelial lineages, as demonstrated by positive Alizarin Red S staining and Ac-LDL uptake. pMSC differentiation in the presence of non-cytotoxic BP concentrations showed that nitrogen containing BPs had a significant inhibitory effect on cell migration and endothelial marker gene expression, as well as compromised endothelial differentiation as demonstrated using von Willebrand factor immunofluorescence staining and tube formation assay. This in vitro study demonstrated that at non-cytotoxic levels, nitrogen-containing BPs inhibit differentiation of pMSCs into cells of an endothelial lineage and affect the downstream functional capability of these cells supporting a multi-modal effect of BPs on angiogenesis as pathogenic mechanism contributing to bone healing disorders such as bisphosphonate related osteonecrosis of the jaws (BRONJ).

Item ID: 44264
Item Type: Article (Research - C1)
ISSN: 2045-2322
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Copyright © 2016, Rights Managed by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit

Funders: Australian Dental Research Foundation (ADRF)
Projects and Grants: ADRF #86-2014
Date Deposited: 16 Jun 2016 00:27
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1105 Dentistry > 110509 Special Needs Dentistry @ 50%
11 MEDICAL AND HEALTH SCIENCES > 1105 Dentistry > 110599 Dentistry not elsewhere classified @ 50%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920113 Oro-Dental Disorders @ 80%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920116 Skeletal System and Disorders (incl. Arthritis) @ 20%
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