Shah, K.M., Orton, P., Mani, N. et al. (2 more authors) (2017) Osteocyte physiology and response to fluid shear stress are impaired following exposure to cobalt and chromium: Implications for bone health following joint replacement. Journal of Orthopaedic Research, 35 (8). pp. 1716-1723. ISSN 0736-0266
Abstract
The effects of metal ion exposure on osteocytes, the most abundant cell type in bone and responsible for coordinating bone remodeling, remain unclear. However, several studies have previously shown that exposure to cobalt (Co(2+) ) and chromium (Cr(3+) ), at concentrations equivalent to those found clinically, affect osteoblast and osteoclast survival and function. In this study, we tested the hypothesis that metal ions would similarly impair the normal physiology of osteocytes. The survival, dendritic morphology and response to fluid shear stress (FSS) of the mature osteocyte-like cell-line MLO-Y4 following exposure to clinically relevant concentrations and combinations of Co and Cr ions was measured in 2D-culture. Exposure of MLO-Y4 cells to metal ions reduced cell number, increased dendrites per cell and increased dendrite length. We found that combinations of metal ions had a greater effect than the individual ions alone, and that Co(2+) had a predominate effect on changes to cell numbers and dendrites. Combined metal ion exposure blunted the responses of the MLO-Y4 cells to FSS, including reducing the intracellular calcium responses and modulation of genes for the osteocyte markers Cx43 and Gp38, and the signaling molecules RANKL and Dkk-1. Finally, we demonstrated that in the late osteoblasts/early osteocytes cell line MLO-A5 that Co(2+) exposure had no effect on mineralization, but Cr(3+) treatment inhibited mineralization in a dose dependent manner, without affecting cell viability. Taken together these data indicate that metal exposure can directly affect osteocyte physiology, with potential implications for bone health including osseointegration of cementless components, and periprosthetic bone remodeling. This article is protected by copyright. All rights reserved.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2016 Wiley. This is an author produced version of a paper subsequently published in the Journal of Orthopaedic Research. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | Osteocytes; bone remodeling; mechanical stimuli; metal ions; osseointegration |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > The Medical School (Sheffield) > Division of Genomic Medicine (Sheffield) > Department of Oncology and Metabolism (Sheffield) The University of Sheffield > Sheffield Teaching Hospitals |
Funding Information: | Funder Grant number ORTHOPAEDIC RESEARCH UK UNSPECIFIED |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 05 Oct 2016 08:59 |
Last Modified: | 14 Nov 2017 10:14 |
Published Version: | http://dx.doi.org/10.1002/jor.23449 |
Status: | Published |
Publisher: | Wiley |
Refereed: | Yes |
Identification Number: | 10.1002/jor.23449 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:105463 |