Periostin Upregulates Wnt/[beta]-Catenin Signaling to Promote the Osteogenesis of CTLA4-Modified Human Bone Marrow-Mesenchymal Stem Cells

The enhanced osteogenesis of mesenchymal stem cells (MSCs) modified by expression of cytotoxic T lymphocyte-associated antigen 4 (CTLA4) has been shown in previous studies, but the mechanism remains unknown. Here we found that the bone repair effect of CTLA4-modified MSCs in demineralized bone matri...

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Veröffentlicht in:Scientific reports 2017-01, Vol.7, p.41634
Hauptverfasser: Zhang, Fei, Luo, Keyu, Rong, Zhigang, Wang, Zhengdong, Luo, Fei, Zhang, Zehua, Sun, Dong, Dong, Shiwu, Xu, Jianzhong, Dai, Fei
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container_start_page 41634
container_title Scientific reports
container_volume 7
creator Zhang, Fei
Luo, Keyu
Rong, Zhigang
Wang, Zhengdong
Luo, Fei
Zhang, Zehua
Sun, Dong
Dong, Shiwu
Xu, Jianzhong
Dai, Fei
description The enhanced osteogenesis of mesenchymal stem cells (MSCs) modified by expression of cytotoxic T lymphocyte-associated antigen 4 (CTLA4) has been shown in previous studies, but the mechanism remains unknown. Here we found that the bone repair effect of CTLA4-modified MSCs in demineralized bone matrix (DBM) in a rabbit radius defect model was significantly better than that observed for unmodified MSCs in DBM or DBM alone, and the periostin (POSTN) expression in CTLA4-modified MSCs was significantly higher than that in unmodified MSCs both in vivo and in vitro. In addition, we also found that treatment of CTLA4-modified MSCs with soluble POSTN could inhibit the glycogen synthase kinase-3β activity and increase β-catenin expression through up-regulation of lipoprotein-related protein-6 phosphorylation to promote osteogenic differentiation, but blocking of integrin αvβ3, a receptor of POSTN, could suppress these effects. Our data demonstrated that POSTN expressed in response to CTLA4 can promote the osteogenesis of xenotransplanted MSCs through interaction with Wnt/β-catenin pathway.
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Here we found that the bone repair effect of CTLA4-modified MSCs in demineralized bone matrix (DBM) in a rabbit radius defect model was significantly better than that observed for unmodified MSCs in DBM or DBM alone, and the periostin (POSTN) expression in CTLA4-modified MSCs was significantly higher than that in unmodified MSCs both in vivo and in vitro. In addition, we also found that treatment of CTLA4-modified MSCs with soluble POSTN could inhibit the glycogen synthase kinase-3β activity and increase β-catenin expression through up-regulation of lipoprotein-related protein-6 phosphorylation to promote osteogenic differentiation, but blocking of integrin αvβ3, a receptor of POSTN, could suppress these effects. 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subjects Bone healing
Bone marrow
Bone matrix
CTLA-4 protein
Cytotoxicity
Glycogen
Glycogen synthase kinase 3
Kinases
Lymphocytes
Mesenchymal stem cells
Mesenchyme
Osteogenesis
Phosphorylation
Radius
Skin & tissue grafts
Stem cells
Wnt protein
Xenografts
β-Catenin
title Periostin Upregulates Wnt/[beta]-Catenin Signaling to Promote the Osteogenesis of CTLA4-Modified Human Bone Marrow-Mesenchymal Stem Cells
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