Bisphosphonate가 인간 골수유래 간엽줄기세포의 증식과 알칼리성 인산분해효소 활성에 미치는 영향
Effects of Bisphosphonates on the Proliferation and the Alkaline Phosphatase Activity of Human Bone Marrow Derived Mesenchymal Stem Cells
정준호, 이백수, 권용대, 오주영, 김영란,
소속 상세정보
정준호 ( Jung Jun-Ho ) - 경희대학교 치의학전문대학원 구강악안면외과학교실
이백수 ( Lee Baek-Soo ) - 경희대학교 치의학전문대학원 구강악안면외과학교실
권용대 ( Kwon Yong-Dae ) - 경희대학교 치의학전문대학원 구강악안면외과학교실
오주영 ( Ohe Joo-Young ) - 경희대학교 치의학전문대학원 구강악안면외과학교실
김영란 ( Kim Young-Ran ) - 경희대학교 치의학전문대학원 구강악안면외과학교실
KMID : 0360120110330010010
Abstract
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.
키워드
Bisphosphonates; Alkaline phosphatase; Human mesenchymal stem cell; Osteoblast differentiation
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