Chromium Oxide Nanoparticle Impaired Osteogenesis and Cellular Response to Mechanical Stimulus

Jian Chen,1,* Jing Ding,1,* Yuanhao Wu,2 Shuqiong Zhang,3 Naisheng Zheng,3 Junyao Yang,3 Jing Xu1 1Department of Paediatric Orthopaedics, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092, People’s Republic of China; 2Biodiscovery Institute, School...

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Autores principales: Chen J, Ding J, Wu Y, Zhang S, Zheng N, Yang J, Xu J
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Publicado: Dove Medical Press 2021
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spelling oai:doaj.org-article:346e356d3c7547bda06782d5b002df452021-12-02T18:55:29ZChromium Oxide Nanoparticle Impaired Osteogenesis and Cellular Response to Mechanical Stimulus1178-2013https://doaj.org/article/346e356d3c7547bda06782d5b002df452021-09-01T00:00:00Zhttps://www.dovepress.com/chromium-oxide-nanoparticle-impaired-osteogenesis-and-cellular-respons-peer-reviewed-fulltext-article-IJNhttps://doaj.org/toc/1178-2013Jian Chen,1,* Jing Ding,1,* Yuanhao Wu,2 Shuqiong Zhang,3 Naisheng Zheng,3 Junyao Yang,3 Jing Xu1 1Department of Paediatric Orthopaedics, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092, People’s Republic of China; 2Biodiscovery Institute, School of Pharmacy, University of Nottingham, Nottingham, UK; 3Department of Clinical Laboratory, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092, People’s Republic of China*These authors contributed equally to this workCorrespondence: Junyao Yang; Jing Xu Email yangjunyao@xinhuamed.com.cn; xujing01@xinhuamed.com.cnBackground: Release of metallic wear particles from hip replacement implants is closely associated with aseptic loosening that affects the functionality and survivorship of the prostheses. Chromium oxide nanoparticles (CrNPs) are the dominant form of the wear particles found in the periprosthetic tissues. Whether CrNPs play a role in the clinically observed particle-induced osteolysis, tissue inflammatory reactions and functional activities of human mesenchymal stem cells (MSCs) remain unknown.Methods: A tibia-defect rat model, cytotoxicity assays and flow cytometry were applied to study the effect of CrNPs on MSCs survival and macrophage inflammatory response. Also, oscillatory fluid flow stimulation was used to analyse the osteogenic differentiation of MSCs while treated by CrNPs. In addition, the influence of CrNPs on MSC biomechanical properties was determined via atomic force microscope (AFM) and fluorescence microscopy.Results: It was found that implantation of CrNPs significantly decreased bone formation in vivo. CrNPs had no obvious effects on inflammatory cytokines release of U937 macrophages. Additionally, CrNPs did not interfere with MSCs osteogenic differentiation under static culture. However, the upregulated osteogenic differentiation of MSCs due to fluid flow stimulation was reduced by CrNPs in a dose-dependent manner. Moreover, osteogenic gene expression of OPN, Cox2 and Rnux2 after mechanical stimulation was also decreased by CrNPs treatments. Furthermore, cell elasticity and adhesion force of MSCs were affected by CrNPs over 3 days of exposure. We further verified that these effects of CrNPs could be associated with its interruption on cell mechanical properties.Conclusion: The results demonstrated that CrNPs impaired cellular response to mechanical stimulus and osteogenesis without noticeable effects on the survival of the human MSCs.Keywords: chromium nanoparticle, human mesenchymal stem cells, osteogenesis, mechanical stimulation, cytoskeletonChen JDing JWu YZhang SZheng NYang JXu JDove Medical Pressarticlechromium nanoparticlehuman mesenchymal stem cellsosteogenesismechanical stimulationcytoskeletonMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 16, Pp 6157-6170 (2021)
institution DOAJ
collection DOAJ
language EN
topic chromium nanoparticle
human mesenchymal stem cells
osteogenesis
mechanical stimulation
cytoskeleton
Medicine (General)
R5-920
spellingShingle chromium nanoparticle
human mesenchymal stem cells
osteogenesis
mechanical stimulation
cytoskeleton
Medicine (General)
R5-920
Chen J
Ding J
Wu Y
Zhang S
Zheng N
Yang J
Xu J
Chromium Oxide Nanoparticle Impaired Osteogenesis and Cellular Response to Mechanical Stimulus
description Jian Chen,1,* Jing Ding,1,* Yuanhao Wu,2 Shuqiong Zhang,3 Naisheng Zheng,3 Junyao Yang,3 Jing Xu1 1Department of Paediatric Orthopaedics, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092, People’s Republic of China; 2Biodiscovery Institute, School of Pharmacy, University of Nottingham, Nottingham, UK; 3Department of Clinical Laboratory, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092, People’s Republic of China*These authors contributed equally to this workCorrespondence: Junyao Yang; Jing Xu Email yangjunyao@xinhuamed.com.cn; xujing01@xinhuamed.com.cnBackground: Release of metallic wear particles from hip replacement implants is closely associated with aseptic loosening that affects the functionality and survivorship of the prostheses. Chromium oxide nanoparticles (CrNPs) are the dominant form of the wear particles found in the periprosthetic tissues. Whether CrNPs play a role in the clinically observed particle-induced osteolysis, tissue inflammatory reactions and functional activities of human mesenchymal stem cells (MSCs) remain unknown.Methods: A tibia-defect rat model, cytotoxicity assays and flow cytometry were applied to study the effect of CrNPs on MSCs survival and macrophage inflammatory response. Also, oscillatory fluid flow stimulation was used to analyse the osteogenic differentiation of MSCs while treated by CrNPs. In addition, the influence of CrNPs on MSC biomechanical properties was determined via atomic force microscope (AFM) and fluorescence microscopy.Results: It was found that implantation of CrNPs significantly decreased bone formation in vivo. CrNPs had no obvious effects on inflammatory cytokines release of U937 macrophages. Additionally, CrNPs did not interfere with MSCs osteogenic differentiation under static culture. However, the upregulated osteogenic differentiation of MSCs due to fluid flow stimulation was reduced by CrNPs in a dose-dependent manner. Moreover, osteogenic gene expression of OPN, Cox2 and Rnux2 after mechanical stimulation was also decreased by CrNPs treatments. Furthermore, cell elasticity and adhesion force of MSCs were affected by CrNPs over 3 days of exposure. We further verified that these effects of CrNPs could be associated with its interruption on cell mechanical properties.Conclusion: The results demonstrated that CrNPs impaired cellular response to mechanical stimulus and osteogenesis without noticeable effects on the survival of the human MSCs.Keywords: chromium nanoparticle, human mesenchymal stem cells, osteogenesis, mechanical stimulation, cytoskeleton
format article
author Chen J
Ding J
Wu Y
Zhang S
Zheng N
Yang J
Xu J
author_facet Chen J
Ding J
Wu Y
Zhang S
Zheng N
Yang J
Xu J
author_sort Chen J
title Chromium Oxide Nanoparticle Impaired Osteogenesis and Cellular Response to Mechanical Stimulus
title_short Chromium Oxide Nanoparticle Impaired Osteogenesis and Cellular Response to Mechanical Stimulus
title_full Chromium Oxide Nanoparticle Impaired Osteogenesis and Cellular Response to Mechanical Stimulus
title_fullStr Chromium Oxide Nanoparticle Impaired Osteogenesis and Cellular Response to Mechanical Stimulus
title_full_unstemmed Chromium Oxide Nanoparticle Impaired Osteogenesis and Cellular Response to Mechanical Stimulus
title_sort chromium oxide nanoparticle impaired osteogenesis and cellular response to mechanical stimulus
publisher Dove Medical Press
publishDate 2021
url https://doaj.org/article/346e356d3c7547bda06782d5b002df45
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