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EFFECTS OF ALENDRONATE AND PAMIDRONATE ON THE PROLIFERATION AND THE ALKALINE PHOSPHATASE ACTIVITY OF HUMAN BONE MARROW DERIVED MESENCHYMAL STEM CELLS  

Kim, Young-Ran (Department of Oral and Maxillofacial Surgery, Kyung Hee University Dental School)
Ryu, Dong-Mok (Department of Oral and Maxillofacial Surgery, Kyung Hee University Dental School)
Kwon, Yong-Dae (Department of Oral and Maxillofacial Surgery, Kyung Hee University Dental School)
Yun, Yong-Pil (Department of oral biology and institute of oral biology, Kyung Hee University Dental School)
Publication Information
Journal of the Korean Association of Oral and Maxillofacial Surgeons / v.35, no.6, 2009 , pp. 397-402 More about this Journal
Abstract
The purpose of this study is to investigate the effects of alendronate and pamidronate on proliferation and the alkaline phosphatase activity of human bone marrow derived mesenchymal stem cells and to relate the results with bisphosphonate related osteonecrosis of the jaw(BRONJ). With the consent of patients with no systemic disease and undergoing iliac bone graft, cancellous bone was collected to obtain human bone marrow derived mesenchymal stem cells through cell culture. 96 well plate were prepared with a concentration of $10^4$cell/ well. Alendronate and pamidronate were added to each well with the concentration of $10^{-6}M$, $10^{-8}M$ and $10^{-10}M$, respectively. Then proliferation capacity of each well was evaluated with the cell counting kit. 24 well plates were prepared with a concentration of $10^5$cell/ml/well and with the bone supplement, alendronate and pamidronate were added with the concentration of $10^{-6}M$, $10^{-8}M$ and $10^{-10}M$, respectively on each plate. The plates were cultured for either 24 or 72 hours. Then the cells were sonicated to measure the alkaline phosphatase activity and protein assay was done to standardize the data for analysis. As the concentration of alendronate or pamidronate added to the culture increased, the proliferation capacity of the cells decreased. However, no statistical significance was found between the group with $10^{-10}M$ of bisphophonate and the control group. Pamidronate was not capable of increasing the alkaline phosphatase activity in all trials. However, alkaline phosphatase activity increased with 24 hours of $10^{-8}M$ of alendronate treatment and with 48 hours of $10^{-10}M$ of alendronate treatment. Cell toxicity increased as the bisphosphonate concentration increased. This seems to be associated with the long half life of bisphosphonate, resulting in high concentration of bisphosphonate in the jaw and thus displaying delayed healing after surgical procedures. Alendronate has shown to increase the alkaline phophatase activity of human bone marrow derived mesenchymal stem cells. However, this data is insufficient to conclude that alendronate facilitates the differentiation of human bone marrow derived mesenchymal stem cells. Further studies on DNA level and animal studies are required to support these results.
Keywords
Bisphosphonate; Cell proliferation; Alkaline phosphatase; Osteonecrosis; Mesenchymal stem cells;
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Times Cited By KSCI : 1  (Citation Analysis)
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