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The effects of zoledronate on the survival and function of human osteoblast-like cells

BACKGROUND: Prolonged bisphosphonate treatment might suppress bone remodeling to the extent that normal bone repair is impaired. While this adverse side effect is usually ascribed to the negative effects of bisphosphonates on osteoclast survival and function, these effects on osteoblasts are still u...

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Autores principales: Huang, Kuo-Chin, Cheng, Chin-Chang, Chuang, Po-Yao, Yang, Tien-Yu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4647641/
https://www.ncbi.nlm.nih.gov/pubmed/26572124
http://dx.doi.org/10.1186/s12891-015-0818-5
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author Huang, Kuo-Chin
Cheng, Chin-Chang
Chuang, Po-Yao
Yang, Tien-Yu
author_facet Huang, Kuo-Chin
Cheng, Chin-Chang
Chuang, Po-Yao
Yang, Tien-Yu
author_sort Huang, Kuo-Chin
collection PubMed
description BACKGROUND: Prolonged bisphosphonate treatment might suppress bone remodeling to the extent that normal bone repair is impaired. While this adverse side effect is usually ascribed to the negative effects of bisphosphonates on osteoclast survival and function, these effects on osteoblasts are still unclear. METHODS: In the current study, we hypothesized that zoledronate (ZOL) at the μM level might present negative effects on osteoblast survival and function. In vitro analyses of proliferation, migration and differentiation were performed on human osteoblast-like cells. RESULTS: Our results revealed that ZOL treatment dose- and time-dependently induced apoptosis of osteoblasts after concentrations had reached 10 μM (p < 0.001). The concentrations at which ZOL inhibited osteoblast migration by 50 % were between 10 and 15 μM. Moreover, there was a dose-dependent reduction in the extent of matrix mineralization, but without a concomitant inhibition of osteogenic differentiation in terms of secreted type I collagen and osteocalcin and of alkaline phosphatase activity per viable cell. Analyses of the expression of osteogenic genes confirmed that ZOL at the μM level had no effects on osteogenic differentiation of osteoblasts. CONCLUSION: We concluded that ZOL at the μM level affected osteoblast survival and migration, but did not affect differentiation. The pathophysiological implications of ZOL at the μM level on skeletal disorders need to be investigated and clarified in the future researches. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12891-015-0818-5) contains supplementary material, which is available to authorized users.
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spelling pubmed-46476412015-11-18 The effects of zoledronate on the survival and function of human osteoblast-like cells Huang, Kuo-Chin Cheng, Chin-Chang Chuang, Po-Yao Yang, Tien-Yu BMC Musculoskelet Disord Research Article BACKGROUND: Prolonged bisphosphonate treatment might suppress bone remodeling to the extent that normal bone repair is impaired. While this adverse side effect is usually ascribed to the negative effects of bisphosphonates on osteoclast survival and function, these effects on osteoblasts are still unclear. METHODS: In the current study, we hypothesized that zoledronate (ZOL) at the μM level might present negative effects on osteoblast survival and function. In vitro analyses of proliferation, migration and differentiation were performed on human osteoblast-like cells. RESULTS: Our results revealed that ZOL treatment dose- and time-dependently induced apoptosis of osteoblasts after concentrations had reached 10 μM (p < 0.001). The concentrations at which ZOL inhibited osteoblast migration by 50 % were between 10 and 15 μM. Moreover, there was a dose-dependent reduction in the extent of matrix mineralization, but without a concomitant inhibition of osteogenic differentiation in terms of secreted type I collagen and osteocalcin and of alkaline phosphatase activity per viable cell. Analyses of the expression of osteogenic genes confirmed that ZOL at the μM level had no effects on osteogenic differentiation of osteoblasts. CONCLUSION: We concluded that ZOL at the μM level affected osteoblast survival and migration, but did not affect differentiation. The pathophysiological implications of ZOL at the μM level on skeletal disorders need to be investigated and clarified in the future researches. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12891-015-0818-5) contains supplementary material, which is available to authorized users. BioMed Central 2015-11-16 /pmc/articles/PMC4647641/ /pubmed/26572124 http://dx.doi.org/10.1186/s12891-015-0818-5 Text en © Huang et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Huang, Kuo-Chin
Cheng, Chin-Chang
Chuang, Po-Yao
Yang, Tien-Yu
The effects of zoledronate on the survival and function of human osteoblast-like cells
title The effects of zoledronate on the survival and function of human osteoblast-like cells
title_full The effects of zoledronate on the survival and function of human osteoblast-like cells
title_fullStr The effects of zoledronate on the survival and function of human osteoblast-like cells
title_full_unstemmed The effects of zoledronate on the survival and function of human osteoblast-like cells
title_short The effects of zoledronate on the survival and function of human osteoblast-like cells
title_sort effects of zoledronate on the survival and function of human osteoblast-like cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4647641/
https://www.ncbi.nlm.nih.gov/pubmed/26572124
http://dx.doi.org/10.1186/s12891-015-0818-5
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