The Effect of Zoledronate on the Differentiation of Human Amniotic Fluid-Derived Mesencymal Stem Cells into Adipocytes / 대한수혈학회지

ABSTRACT

BACKGROUND: Amniotic fluid is a rich source of fetal mesenchymal stem cells (MSCs). However, little is known about whether bisphosphonates affect the differentiation into adipocytes. Therefore, this study was aimed to investigate whether zoledronate influences the differentiation of AFMSCs into adipocytes. METHODS: Amniotic fluid cells samples were obtained from 6 pregnant women by second trimester amniocentesis for performing fetal karyotyping. The cells were treated with various concentration (10(-10), 10(-8), 10(-6) M) of zoledronate and the cells were analyzed over 21 days of culture. Differentiation into adipocytes was determined by oil-red O staining and for fatty acid synthase (FAS), acetyl CoA carboxylase 1 (ACC1) and sterol regulatory elementary binding protein-1 (SREBP-1). RESULTS: Differentiation of AFMSCs into adipocytes was found by oil-red O staining. Zoledronate influenced the differentiation of AFMSCs into adipocytes in a dose- and time-dependent manner. At 7 days of culture, the expressions of FAS and SREBP-1 showed no significant differences compared to that of the control regardless of the dose of zoledronate. Very little ACC1 expression was found. However, the expressions of these three markers were remarkably increased at 14 days of culture. Of them, the ACC1 expression was significantly increased by 10(-8) M and 10(-6) M of zoledronate. At 21 days of culture, there were no effects of zoledronate on the expressions of FAS and SREBP-1. However, the ACC1 expression was decreased with an increasing dose of zoledronate (P<.05). CONCLUSION: This study shows that AFMSCs can be differentiated into adipocytes. The induction of this differentiation following zoledronate treatment appears to be dose dependent and time-of-culture dependent.