Gadolinium-doped bioglass scaffolds promote osteogenic differentiation of hBMSC via the Akt/GSK3β pathway and facilitate bone repair in vivo

Dao-Yu Zhu,1,* Bin Lu,2,* Jun-Hui Yin,1 Qin-Fei Ke,2 He Xu,2 Chang-Qing Zhang,1 Ya-Ping Guo,2 You-Shui Gao1,3 1Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, China; 2The Education Ministry Key Lab of Resource Chemistry,...

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Autores principales: Zhu DY, Lu B, Yin JH, Ke QF, Xu H, Zhang CQ, Guo YP, Gao YS
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Publicado: Dove Medical Press 2019
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spelling oai:doaj.org-article:2ddca4fe67e04fc4ae6d4bba90d2760a2021-12-02T01:43:58ZGadolinium-doped bioglass scaffolds promote osteogenic differentiation of hBMSC via the Akt/GSK3β pathway and facilitate bone repair in vivo1178-2013https://doaj.org/article/2ddca4fe67e04fc4ae6d4bba90d2760a2019-02-01T00:00:00Zhttps://www.dovepress.com/gadolinium-doped-bioglass-scaffolds-promote-osteogenic-differentiation-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Dao-Yu Zhu,1,* Bin Lu,2,* Jun-Hui Yin,1 Qin-Fei Ke,2 He Xu,2 Chang-Qing Zhang,1 Ya-Ping Guo,2 You-Shui Gao1,3 1Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, China; 2The Education Ministry Key Lab of Resource Chemistry, Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Normal University, Shanghai 200234, China; 3Centre for Orthopaedic Research, Faculty of Health and Medical Sciences, The University of Western Australia, Perth, WA 6009, Australia *These authors contributed equally to this work Background: Biomaterial-induced osteogenesis is mainly related to hierarchically porous structures and bioactive components. Rare earth elements are well known to promote osteogenesis and stimulate bone repair; however, the underlying biological effects of gadolinium (Gd) element on bone regeneration are not yet known. Methods: In this study, we successfully fabricated gadolinium-doped bioglass (Gd-BG) scaffolds by combining hollow mesoporous Gd-BG microspheres with chitosan and evaluated in vitro effects and underlying mechanisms with Cell Counting Kit-8, scanning electron microscopy, alkaline phosphatase, Alizarin red staining, and polymerase chain reaction. Cranial defect model of rats was constructed to evaluate their in vivo effects. Results: The results indicated that Gd-BG scaffolds could promote the proliferation and osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs). Mechanistically, the Akt/GSK3β signaling pathway was activated by the Gd-BG scaffolds. The enhancing effect of Gd-BG scaffolds on the osteogenic differentiation of hBMSCs was inhibited by the addition of LY294002, an inhibitor of Akt. Moreover, the in vivo cranial defect model of rats indicated that the Gd-BG scaffolds could effectively promote bone regeneration. Conclusion: Both in vitro and in vivo results suggested that Gd-BG scaffolds have promising applications in bone tissue engineering. Keywords: bone scaffold, gadolinium, Akt/GSK3β pathway, bone regenerationZhu DYLu BYin JHKe QFXu HZhang CQGuo YPGao YSDove Medical Pressarticlebone scaffoldgadoliniumAkt/GSK3β pathwaybone regenerationMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 1085-1100 (2019)
institution DOAJ
collection DOAJ
language EN
topic bone scaffold
gadolinium
Akt/GSK3β pathway
bone regeneration
Medicine (General)
R5-920
spellingShingle bone scaffold
gadolinium
Akt/GSK3β pathway
bone regeneration
Medicine (General)
R5-920
Zhu DY
Lu B
Yin JH
Ke QF
Xu H
Zhang CQ
Guo YP
Gao YS
Gadolinium-doped bioglass scaffolds promote osteogenic differentiation of hBMSC via the Akt/GSK3β pathway and facilitate bone repair in vivo
description Dao-Yu Zhu,1,* Bin Lu,2,* Jun-Hui Yin,1 Qin-Fei Ke,2 He Xu,2 Chang-Qing Zhang,1 Ya-Ping Guo,2 You-Shui Gao1,3 1Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, China; 2The Education Ministry Key Lab of Resource Chemistry, Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Normal University, Shanghai 200234, China; 3Centre for Orthopaedic Research, Faculty of Health and Medical Sciences, The University of Western Australia, Perth, WA 6009, Australia *These authors contributed equally to this work Background: Biomaterial-induced osteogenesis is mainly related to hierarchically porous structures and bioactive components. Rare earth elements are well known to promote osteogenesis and stimulate bone repair; however, the underlying biological effects of gadolinium (Gd) element on bone regeneration are not yet known. Methods: In this study, we successfully fabricated gadolinium-doped bioglass (Gd-BG) scaffolds by combining hollow mesoporous Gd-BG microspheres with chitosan and evaluated in vitro effects and underlying mechanisms with Cell Counting Kit-8, scanning electron microscopy, alkaline phosphatase, Alizarin red staining, and polymerase chain reaction. Cranial defect model of rats was constructed to evaluate their in vivo effects. Results: The results indicated that Gd-BG scaffolds could promote the proliferation and osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs). Mechanistically, the Akt/GSK3β signaling pathway was activated by the Gd-BG scaffolds. The enhancing effect of Gd-BG scaffolds on the osteogenic differentiation of hBMSCs was inhibited by the addition of LY294002, an inhibitor of Akt. Moreover, the in vivo cranial defect model of rats indicated that the Gd-BG scaffolds could effectively promote bone regeneration. Conclusion: Both in vitro and in vivo results suggested that Gd-BG scaffolds have promising applications in bone tissue engineering. Keywords: bone scaffold, gadolinium, Akt/GSK3β pathway, bone regeneration
format article
author Zhu DY
Lu B
Yin JH
Ke QF
Xu H
Zhang CQ
Guo YP
Gao YS
author_facet Zhu DY
Lu B
Yin JH
Ke QF
Xu H
Zhang CQ
Guo YP
Gao YS
author_sort Zhu DY
title Gadolinium-doped bioglass scaffolds promote osteogenic differentiation of hBMSC via the Akt/GSK3β pathway and facilitate bone repair in vivo
title_short Gadolinium-doped bioglass scaffolds promote osteogenic differentiation of hBMSC via the Akt/GSK3β pathway and facilitate bone repair in vivo
title_full Gadolinium-doped bioglass scaffolds promote osteogenic differentiation of hBMSC via the Akt/GSK3β pathway and facilitate bone repair in vivo
title_fullStr Gadolinium-doped bioglass scaffolds promote osteogenic differentiation of hBMSC via the Akt/GSK3β pathway and facilitate bone repair in vivo
title_full_unstemmed Gadolinium-doped bioglass scaffolds promote osteogenic differentiation of hBMSC via the Akt/GSK3β pathway and facilitate bone repair in vivo
title_sort gadolinium-doped bioglass scaffolds promote osteogenic differentiation of hbmsc via the akt/gsk3β pathway and facilitate bone repair in vivo
publisher Dove Medical Press
publishDate 2019
url https://doaj.org/article/2ddca4fe67e04fc4ae6d4bba90d2760a
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