화학공학소재연구정보센터
Biochemical and Biophysical Research Communications, Vol.513, No.2, 386-391, 2019
A cellular model for Wilson's disease using patient-derived induced pluripotent stem cells revealed aberrant beta-catenin pathway during osteogenesis
Wilson's disease (WD) is a rare autosomal recessive disorder of copper metabolism caused by an ATP7B gene mutation. Except for hepatic, neurological symptoms, lower bone mineral density is another most frequent clinical features of WD, but the underlying mechanisms have not been fully understood. This article aims to use induced pluripotent stem cells (iPSCs) to establish cellular osteoblasts model related to WD to identify abnormal osteogenesis and signaling pathways. In this study, we successfully produced functional osteoblasts from normal and WD iPSCs through embryoid bodies (EBs) formation method, and then we found WD osteoblasts may have a lower osteogenesis activity than normal controls by detection of osteogenic marker genes and mineralization ability. Further, through gene expression profiling, detection of beta-catenin in total protein and nuclear protein, and the nuclear localization of beta-catenin, we identified and validated that low osteogenic activity in WD may be due to abnormal beta-catenin pathway. Interestingly, we found SKL2001, a small molecule can reverse decreased osteogenesis of WD. In summery, our results suggested that the low bone density of WD may caused by abnormal beta-catenin signaling pathway, and these may provided a new target for the treatment of WD. (C) 2019 Published by Elsevier Inc.