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Rebamipide Delivered by Brushite Cement Enhances Osteoblast and Macrophage Proliferation

Many of the bioactive agents capable of stimulating osseous regeneration, such as bone morphogenetic protein-2 (BMP-2) or prostaglandin E2 (PGE2), are limited by rapid degradation, a short bioactive half-life at the target site in vivo, or are prohibitively expensive to obtain in large quantities. R...

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Autores principales: Pujari-Palmer, Michael, Pujari-Palmer, Shiuli, Engqvist, Håkan, Karlsson Ott, Marjam
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4449171/
https://www.ncbi.nlm.nih.gov/pubmed/26023912
http://dx.doi.org/10.1371/journal.pone.0128324
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author Pujari-Palmer, Michael
Pujari-Palmer, Shiuli
Engqvist, Håkan
Karlsson Ott, Marjam
author_facet Pujari-Palmer, Michael
Pujari-Palmer, Shiuli
Engqvist, Håkan
Karlsson Ott, Marjam
author_sort Pujari-Palmer, Michael
collection PubMed
description Many of the bioactive agents capable of stimulating osseous regeneration, such as bone morphogenetic protein-2 (BMP-2) or prostaglandin E2 (PGE2), are limited by rapid degradation, a short bioactive half-life at the target site in vivo, or are prohibitively expensive to obtain in large quantities. Rebamipide, an amino acid modified hydroxylquinoline, can alter the expression of key mediators of bone anabolism, cyclo-oxygenase 2 (COX-2), BMP-2 and vascular endothelial growth factor (VEGF), in diverse cell types such as mucosal and endothelial cells or chondrocytes. The present study investigates whether Rebamipide enhances proliferation and differentiation of osteoblasts when delivered from brushite cement. The reactive oxygen species (ROS) quenching ability of Rebampide was tested in macrophages as a measure of bioactivity following drug release incubation times, up to 14 days. Rebamipide release from brushite occurrs via non-fickian diffusion, with a rapid linear release of 9.70% ±0.37% of drug per day for the first 5 days, and an average of 0.5%-1% per day thereafter for 30 days. Rebamipide slows the initial and final cement setting time by up to 3 and 1 minute, respectively, but does not significantly reduce the mechanical strength below 4% (weight percentage). Pre-osteoblast proliferation increases by 24% upon exposure to 0.4uM Rebamipide, and by up to 73% when Rebamipide is delivered via brushite cement. Low doses of Rebamipide do not adversely affect peak alkaline phosphatase activity in differentiating pre-osteoblasts. Rebamipide weakly stimulates proliferation in macrophages at low concentrations (118 ±7.4% at 1uM), and quenches ROS by 40-60%. This is the first investigation of Rebamipide in osteoblasts.
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spelling pubmed-44491712015-06-09 Rebamipide Delivered by Brushite Cement Enhances Osteoblast and Macrophage Proliferation Pujari-Palmer, Michael Pujari-Palmer, Shiuli Engqvist, Håkan Karlsson Ott, Marjam PLoS One Research Article Many of the bioactive agents capable of stimulating osseous regeneration, such as bone morphogenetic protein-2 (BMP-2) or prostaglandin E2 (PGE2), are limited by rapid degradation, a short bioactive half-life at the target site in vivo, or are prohibitively expensive to obtain in large quantities. Rebamipide, an amino acid modified hydroxylquinoline, can alter the expression of key mediators of bone anabolism, cyclo-oxygenase 2 (COX-2), BMP-2 and vascular endothelial growth factor (VEGF), in diverse cell types such as mucosal and endothelial cells or chondrocytes. The present study investigates whether Rebamipide enhances proliferation and differentiation of osteoblasts when delivered from brushite cement. The reactive oxygen species (ROS) quenching ability of Rebampide was tested in macrophages as a measure of bioactivity following drug release incubation times, up to 14 days. Rebamipide release from brushite occurrs via non-fickian diffusion, with a rapid linear release of 9.70% ±0.37% of drug per day for the first 5 days, and an average of 0.5%-1% per day thereafter for 30 days. Rebamipide slows the initial and final cement setting time by up to 3 and 1 minute, respectively, but does not significantly reduce the mechanical strength below 4% (weight percentage). Pre-osteoblast proliferation increases by 24% upon exposure to 0.4uM Rebamipide, and by up to 73% when Rebamipide is delivered via brushite cement. Low doses of Rebamipide do not adversely affect peak alkaline phosphatase activity in differentiating pre-osteoblasts. Rebamipide weakly stimulates proliferation in macrophages at low concentrations (118 ±7.4% at 1uM), and quenches ROS by 40-60%. This is the first investigation of Rebamipide in osteoblasts. Public Library of Science 2015-05-29 /pmc/articles/PMC4449171/ /pubmed/26023912 http://dx.doi.org/10.1371/journal.pone.0128324 Text en © 2015 Pujari-Palmer et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Pujari-Palmer, Michael
Pujari-Palmer, Shiuli
Engqvist, Håkan
Karlsson Ott, Marjam
Rebamipide Delivered by Brushite Cement Enhances Osteoblast and Macrophage Proliferation
title Rebamipide Delivered by Brushite Cement Enhances Osteoblast and Macrophage Proliferation
title_full Rebamipide Delivered by Brushite Cement Enhances Osteoblast and Macrophage Proliferation
title_fullStr Rebamipide Delivered by Brushite Cement Enhances Osteoblast and Macrophage Proliferation
title_full_unstemmed Rebamipide Delivered by Brushite Cement Enhances Osteoblast and Macrophage Proliferation
title_short Rebamipide Delivered by Brushite Cement Enhances Osteoblast and Macrophage Proliferation
title_sort rebamipide delivered by brushite cement enhances osteoblast and macrophage proliferation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4449171/
https://www.ncbi.nlm.nih.gov/pubmed/26023912
http://dx.doi.org/10.1371/journal.pone.0128324
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