Osteogenic differentiation of mesenchymal stem cells is affected by alendronate

Petcu, E., Sharma, D., Hamlet, S., and Ivanovski, S. (2015) Osteogenic differentiation of mesenchymal stem cells is affected by alendronate. Tissue Engineering Part A, 21 (S1). pp. 348-349.

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Abstract

Objectives: Various conditions like osteoporosis and Paget’s disease show altered bone homeostasis skewed towards increased resorption warranting use of anti-resorptive drugs like Alendronate (nitrogen-containing bisphosphonate). However, a prominent side effect of alendronate is medication induced osteonecrosis of jawbone (previously termed BRONJ). Although in-vitro and in-vivo studies have shown that Alendronate affects bone cells, gingival fibroblasts and local vascularity, literature evaluating the influence of alendronate on pluripotent stem cells is distinctly lacking. Thus, our in-vitro study was aimed at evaluating the effects of alendronate on the proliferation, osteogenic differentiation and mineralization potential of human mesenchymal stem cells (MSCs).

Methods: MSCs were cultured in-vitro with alendronate at0.25 mM, 0.5 mM, 1 mM, 2 mM and 3 mM in culture media for 10 days and proliferation was assessed using an Alamar Blue assay. Live-Dead assay was used to determine a suitable concentration for the differentiation assay. Osteogenic differentiation was conducted in osteogenic media over 21 days and Alizarin Red staining was undertaken to confirm mineralization and quantify the staining.

Results: Alamar Blue assay showed that Alendronate was cytotoxicat 2 mM and 3 mM. Optimal alendronate concentration for differentiation of MSCs without causing cell death was 1 mM, as confirmed by the Live-Dead assay. Subsequently, differentiation assay and Alizarin red staining showed mineralization occurred at 21days in differentiation media. Quantification showed that Alendronate significantly affected the functional aspect of differentiated MSCs.

Significance: These findings suggest direct effects of alendronate on MSCs could have a significant role in inhibiting optimal bone remodelling and mineralization thereby ensuing MRONJ.

Item ID: 47571
Item Type: Article (Abstract)
ISSN: 2152-4947
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Funders: Australian Dental Research Foundation (ADRF)
Date Deposited: 13 Sep 2017 01:35
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 @ 25%
10 TECHNOLOGY > 1004 Medical Biotechnology > 100404 Regenerative Medicine (incl Stem Cells and Tissue Engineering) @ 25%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920113 Oro-Dental Disorders @ 75%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920116 Skeletal System and Disorders (incl. Arthritis) @ 25%
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