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6-bromoindirubin-3’-oxime promotes osteogenic differentiation of canine BMSCs through inhibition of GSK3β activity and activation of the Wnt/β-catenin signaling pathway

Zhao, Xiao E. ; Yang, Zhenshan LU orcid ; Gao, Zhen ; Ge, Junbang ; Wei, Qing and Ma, Baohua (2019) In Anais da Academia Brasileira de Ciencias 91(1). p.1-14
Abstract

This study aimed to investigate how 6-bromoindirubin-3’-oxime (BIO) increases the osteogenic differentiation of canine bone mesenchymal stem cells (BMSCs) and the role of the Wnt/β-catenin signaling pathway in this process. We mimicked the effect of Wnt by adding BIO to the culture medium of BMSCs and examined whether canonical Wnt signaling positively affects the differentiation of these cells into osteoblasts. Canine BMSCs were cultured with 0.5 and 1.0 μM BIO under osteogenic conditions and then differentiation markers were investigated. It was found that BIO significantly increased the activity of alkaline phosphatase (ALP), the number of ALP-positive cells, the mineralization level and calcium deposits. Moreover, cells cultured... (More)

This study aimed to investigate how 6-bromoindirubin-3’-oxime (BIO) increases the osteogenic differentiation of canine bone mesenchymal stem cells (BMSCs) and the role of the Wnt/β-catenin signaling pathway in this process. We mimicked the effect of Wnt by adding BIO to the culture medium of BMSCs and examined whether canonical Wnt signaling positively affects the differentiation of these cells into osteoblasts. Canine BMSCs were cultured with 0.5 and 1.0 μM BIO under osteogenic conditions and then differentiation markers were investigated. It was found that BIO significantly increased the activity of alkaline phosphatase (ALP), the number of ALP-positive cells, the mineralization level and calcium deposits. Moreover, cells cultured with 0.5 and 1.0 μM BIO exhibited detectable β-catenin expression in their nuclei, and showed upregulated β-catenin and glycogen synthase kinase 3 beta(GSK3β) phosphorylation compared to untreated cells. In addition, BIO enhanced the mRNA expression of osteoblast differentiation markers such as ALP, runt-related transcription factor 2, collagen I, osteocalcin, and osteonectin. In conclusion, BIO upregulated GSK3β phosphorylation and inhibited its activity, thereby activating the Wnt/β-catenin signaling pathway and promoting the osteogenic differentiation of canine BMSCs. The effect of 1.0 μM BIO on BMSCs differentiation was stronger than that of 0.5 μM BIO.

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author
; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
keywords
Bone mesenchymal stem cells, Bromoindirubin oxime, Canine, Osteogenetic differentiation
in
Anais da Academia Brasileira de Ciencias
volume
91
issue
1
article number
e20180459
pages
1 - 14
publisher
Academia Brasileira de Ciencias
external identifiers
  • pmid:30916158
  • scopus:85063941063
ISSN
0001-3765
DOI
10.1590/0001-3765201920180459
language
English
LU publication?
no
additional info
Publisher Copyright: © 2019, Academia Brasileira de Ciencias. All rights reserved.
id
eae6ee80-0d36-41f0-865a-4f4054b3acd2
date added to LUP
2024-02-28 14:54:22
date last changed
2024-03-01 03:35:59
@article{eae6ee80-0d36-41f0-865a-4f4054b3acd2,
  abstract     = {{<p>This study aimed to investigate how 6-bromoindirubin-3’-oxime (BIO) increases the osteogenic differentiation of canine bone mesenchymal stem cells (BMSCs) and the role of the Wnt/β-catenin signaling pathway in this process. We mimicked the effect of Wnt by adding BIO to the culture medium of BMSCs and examined whether canonical Wnt signaling positively affects the differentiation of these cells into osteoblasts. Canine BMSCs were cultured with 0.5 and 1.0 μM BIO under osteogenic conditions and then differentiation markers were investigated. It was found that BIO significantly increased the activity of alkaline phosphatase (ALP), the number of ALP-positive cells, the mineralization level and calcium deposits. Moreover, cells cultured with 0.5 and 1.0 μM BIO exhibited detectable β-catenin expression in their nuclei, and showed upregulated β-catenin and glycogen synthase kinase 3 beta(GSK3β) phosphorylation compared to untreated cells. In addition, BIO enhanced the mRNA expression of osteoblast differentiation markers such as ALP, runt-related transcription factor 2, collagen I, osteocalcin, and osteonectin. In conclusion, BIO upregulated GSK3β phosphorylation and inhibited its activity, thereby activating the Wnt/β-catenin signaling pathway and promoting the osteogenic differentiation of canine BMSCs. The effect of 1.0 μM BIO on BMSCs differentiation was stronger than that of 0.5 μM BIO.</p>}},
  author       = {{Zhao, Xiao E. and Yang, Zhenshan and Gao, Zhen and Ge, Junbang and Wei, Qing and Ma, Baohua}},
  issn         = {{0001-3765}},
  keywords     = {{Bone mesenchymal stem cells; Bromoindirubin oxime; Canine; Osteogenetic differentiation}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{1--14}},
  publisher    = {{Academia Brasileira de Ciencias}},
  series       = {{Anais da Academia Brasileira de Ciencias}},
  title        = {{6-bromoindirubin-3’-oxime promotes osteogenic differentiation of canine BMSCs through inhibition of GSK3β activity and activation of the Wnt/β-catenin signaling pathway}},
  url          = {{http://dx.doi.org/10.1590/0001-3765201920180459}},
  doi          = {{10.1590/0001-3765201920180459}},
  volume       = {{91}},
  year         = {{2019}},
}