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KMID : 0360120110330010010
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Journal of the Korean Society of Maxillofacial Plastic Reconstructive Surgeons
2011 Volume.33 No. 1 p.10 ~ p.18
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Effects of Bisphosphonates on the Proliferation and the Alkaline Phosphatase Activity of Human Bone Marrow Derived Mesenchymal Stem Cells
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Jung Jun-Ho
Lee Baek-Soo
Kwon Yong-Dae
Ohe Joo-Young
Kim Young-Ran
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Abstract
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Purpose: The purpose of this study is to find out the effects of bisphosphonates (BPs) on the proliferation and the alkaline phosphatase (ALP) activity of human bone marrow derived mesenchymal stem cells (hMSCs), and thus state its correlation with bisphosphonate related osteonecrosis of the jaw (BRONJ).
Methods: hMSCs was obtained by collecting and culturing cancellous bone fragments from a patient undergoing iliac bone graft. Alendronate (Aln) and Pamidronate (Pam), Ibandronate (Ibn) were added to the culture media in the concentration from 10-3 M to 10-11 M and cell toxicity, viability were measured. For ALP activity evaluation, Aln and Pam were added to the culture media in the concentration from 5×10-7 M to 1×10-8 M and were cultured for 1 week, 2 weeks and 3 weeks. ALP activity data were standardized using protein assay. Control groups were prepared for each examination.
Results: Aln, Pam and Ibn all failed to increase the proliferation of hMSCs. With 1 week, 2 weeks of 5×10-8 M of Aln treatment, the ALP activity increased. Pam treatment increased the ALP activity with 2 weeks of 5×10-8 M and 1×10-8 M. Also Ibn treatment increased the ALP activity with 2 weeks of 5×10-8 M and 1×10-8 M.
Conclusion: It is considered that BPs are not capable of improving the proliferation of hMSCs. Also, after a transient increase in the ALP activity with the lower concentration of BPs, the activity decreased again. Therefore, in patients on long-term medication of BPs, the proliferation and osteoblast differentiation of hMSCs are restrained, and thus delayed wound healing and increase in BRONJ complications may occur.
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KEYWORD
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Bisphosphonates, Alkaline phosphatase, Human mesenchymal stem cell, Osteoblast differentiation
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