Effects of immunosuppressants, FK506 and cyclosporin A, on the osteogenic differentiation of rat mesenchymal stem cells
변유경, 김경화, 김수환, 김영성, 구기태, 김태일, 설양조, 구영, 류인철, 이용무,
소속 상세정보
변유경 ( Byun Yu-Kyung ) - Seoul National University School of Dentistry Department of Periodontology
김경화 ( Kim Kyoung-Hwa ) - Seoul National University School of Dentistry Department of Periodontology
김수환 ( Kim Su-Hwan ) - Asan Medical Center Department of Periodontics
김영성 ( Kim Young-Sung ) - Asan Medical Center Department of Periodontics
구기태 ( Koo Ki-Tae ) - Seoul National University School of Dentistry Department of Periodontology
김태일 ( Kim Tai-Il ) - Seoul National University School of Dentistry Department of Periodontology
설양조 ( Seol Yang-Jo ) - Seoul National University School of Dentistry Department of Periodontology
구영 ( Ku Young ) - Seoul National University School of Dentistry Department of Periodontology
류인철 ( Rhyu In-Chul ) - Seoul National University School of Dentistry Department of Periodontology
이용무 ( Lee Yong-Moo ) - Seoul National University School of Dentistry Department of Periodontology
KMID : 0363020120420030073
Abstract
Purpose: The purpose of this study was to investigate the effects of the immunosuppressants FK506 and cyclosporin A (CsA) on the osteogenic differentiation of rat mesenchymal stem cells (MSCs).
Methods: The effect of FK506 and CsA on rat MSCs was assessed in vitro. The MTT assay was used to determine the deleterious effect of immunosuppressants on stem cell proliferation at 1, 3, and 7 days. Alkaline phosphatase (ALP) activity was analyzed on days 3, 7, and 14. Alizarin red S staining was done on day 21 to check mineralization nodule formation. Real-time polymerase chain reaction (RT-PCR) was also performed to detect the expressions of bone tissue-specific genes on days 1 and 7.
Results: Cell proliferation was promoted more in the FK506 groups than the control or CsA groups on days 3 and 7. The FK506 groups showed increased ALP activity compared to the other groups during the experimental period. The ALP activity of the CsA groups did not differ from the control group in any of the assessments. Mineralization nodule formation was most prominent in the FK506 groups at 21 days. RT-PCR results of the FK506 groups showed that several bone-related genes-osteopontin, osteonectin, and type I collagen (Col-I)-were expressed more than the control in the beginning, but the intensity of expression decreased over time. Runx2 and Dlx5 gene expression were up-regulated on day 7. The effects of 50 nM CsA on osteonectin and Col-I were similar to those of the FK506 groups, but in the 500 nM CsA group, most of the genes were less expressed compared to the control.
Conclusions: These results suggest that FK506 enhances the osteoblastic differentiation of rat MSCs. Therefore, FK506 might have a beneficial effect on bone regeneration when immunosuppressants are needed in xenogenic or allogenic stem cell transplantation to treat bone defects.
키워드
Cell differentiation ; Cyclosporin A ; FK506 ; Immunosuppressive agents ; Mesenchymal stem cells
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