1. Academic Validation
  2. A cellular model for Wilson's disease using patient-derived induced pluripotent stem cells revealed aberrant β-catenin pathway during osteogenesis

A cellular model for Wilson's disease using patient-derived induced pluripotent stem cells revealed aberrant β-catenin pathway during osteogenesis

  • Biochem Biophys Res Commun. 2019 May 28;513(2):386-391. doi: 10.1016/j.bbrc.2019.04.013.
Jing Liu 1 Yazhou Cui 2 Liang Shi 2 Jing Luan 2 Xiaoyan Zhou 2 Jinxiang Han 3
Affiliations

Affiliations

  • 1 School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Ji'nan, Shandong, China; Shandong Medical Biotechnological Center, Shandong Academy of Medical Sciences, Key Laboratory for Rare Disease Research of Shandong Province, Ji'nan, Shandong, China.
  • 2 Shandong Medical Biotechnological Center, Shandong Academy of Medical Sciences, Key Laboratory for Rare Disease Research of Shandong Province, Ji'nan, Shandong, China.
  • 3 School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Ji'nan, Shandong, China. Electronic address: jxhan9888@aliyun.com.
Abstract

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 β-catenin in total protein and nuclear protein, and the nuclear localization of β-catenin, we identified and validated that low osteogenic activity in WD may be due to abnormal β-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 β-catenin signaling pathway, and these may provided a new target for the treatment of WD.

Keywords

Osteoblast; SKL2001; Wilson's disease; iPSCs; β-catenin.

Figures
Products