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Effects of Strontium-Doped β-Tricalcium Scaffold on Longitudinal Nuclear Factor-Kappa Beta and Vascular Endothelial Growth Factor Receptor-2 Promoter Activities during Healing in a Murine Critical-Size Bone Defect Model
It was hypothesized that strontium (Sr)-doped β-tricalcium phosphate (TCP)-based scaffolds have a positive effect on the regeneration of large bone defects (LBD). Readouts in our mice models were nuclear factor-kappa beta (NF-κB) activity and vascular endothelial growth factor receptor-2 (VEGFR-2) p...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246816/ https://www.ncbi.nlm.nih.gov/pubmed/32370039 http://dx.doi.org/10.3390/ijms21093208 |
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author | Tohidnezhad, Mersedeh Kubo, Yusuke Lichte, Philipp Heigl, Tobias Roch, Diana Barahmand Pour, Nazanin Bergmann, Christian Sönmez, Tolga Taha Hock, Jennifer Vanessa Phi Fragoulis, Athanassios Gremse, Felix Rosenhain, Stefanie Slowik, Alexander Bienert, Michaela Kweider, Nisreen Wruck, Christoph Jan Jahr, Holger Hildebrand, Frank Pape, Hans Christoph Neuß, Sabine Fischer, Horst Pufe, Thomas |
author_facet | Tohidnezhad, Mersedeh Kubo, Yusuke Lichte, Philipp Heigl, Tobias Roch, Diana Barahmand Pour, Nazanin Bergmann, Christian Sönmez, Tolga Taha Hock, Jennifer Vanessa Phi Fragoulis, Athanassios Gremse, Felix Rosenhain, Stefanie Slowik, Alexander Bienert, Michaela Kweider, Nisreen Wruck, Christoph Jan Jahr, Holger Hildebrand, Frank Pape, Hans Christoph Neuß, Sabine Fischer, Horst Pufe, Thomas |
author_sort | Tohidnezhad, Mersedeh |
collection | PubMed |
description | It was hypothesized that strontium (Sr)-doped β-tricalcium phosphate (TCP)-based scaffolds have a positive effect on the regeneration of large bone defects (LBD). Readouts in our mice models were nuclear factor-kappa beta (NF-κB) activity and vascular endothelial growth factor receptor-2 (VEGFR-2) promoter activity during the healing process. A 2-mm critical-size femoral fracture was performed in transgenic NF-κB- and VEGFR-2-luciferase reporter mice. The fracture was filled with a 3D-printed β-TCP scaffold with or without Sr. A bioluminescence in-vivo imaging system was used to sequentially investigate NF-κB and VEGFR-2 expression for two months. After sacrifice, soft and osseous tissue formation in the fracture sites was histologically examined. NF-κB activity increased in the β-TCP + Sr group in the latter stage (day 40–60). VEGFR-2 activity increased in the + Sr group from days 0–15 but decreased and showed significantly less activity than the β-TCP and non-scaffold groups from days 40–60. The new bone formation and soft tissue formation in the + Sr group were significantly higher than in the β-TCP group, whereas the percentage of osseous tissue formation in the β-TCP group was significantly higher than in the β-TCP + Sr group. We analyzed longitudinal VEGFR-2 promoter activity and NF-κB activity profiles, as respective agents of angiogenesis and inflammation, during LBD healing. The extended inflammation phase and eventually more rapid resorption of scaffold caused by the addition of strontium accelerates temporary bridging of the fracture gaps. This finding has the potential to inform an improved treatment strategy for patients who suffer from osteoporosis. |
format | Online Article Text |
id | pubmed-7246816 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-72468162020-06-10 Effects of Strontium-Doped β-Tricalcium Scaffold on Longitudinal Nuclear Factor-Kappa Beta and Vascular Endothelial Growth Factor Receptor-2 Promoter Activities during Healing in a Murine Critical-Size Bone Defect Model Tohidnezhad, Mersedeh Kubo, Yusuke Lichte, Philipp Heigl, Tobias Roch, Diana Barahmand Pour, Nazanin Bergmann, Christian Sönmez, Tolga Taha Hock, Jennifer Vanessa Phi Fragoulis, Athanassios Gremse, Felix Rosenhain, Stefanie Slowik, Alexander Bienert, Michaela Kweider, Nisreen Wruck, Christoph Jan Jahr, Holger Hildebrand, Frank Pape, Hans Christoph Neuß, Sabine Fischer, Horst Pufe, Thomas Int J Mol Sci Article It was hypothesized that strontium (Sr)-doped β-tricalcium phosphate (TCP)-based scaffolds have a positive effect on the regeneration of large bone defects (LBD). Readouts in our mice models were nuclear factor-kappa beta (NF-κB) activity and vascular endothelial growth factor receptor-2 (VEGFR-2) promoter activity during the healing process. A 2-mm critical-size femoral fracture was performed in transgenic NF-κB- and VEGFR-2-luciferase reporter mice. The fracture was filled with a 3D-printed β-TCP scaffold with or without Sr. A bioluminescence in-vivo imaging system was used to sequentially investigate NF-κB and VEGFR-2 expression for two months. After sacrifice, soft and osseous tissue formation in the fracture sites was histologically examined. NF-κB activity increased in the β-TCP + Sr group in the latter stage (day 40–60). VEGFR-2 activity increased in the + Sr group from days 0–15 but decreased and showed significantly less activity than the β-TCP and non-scaffold groups from days 40–60. The new bone formation and soft tissue formation in the + Sr group were significantly higher than in the β-TCP group, whereas the percentage of osseous tissue formation in the β-TCP group was significantly higher than in the β-TCP + Sr group. We analyzed longitudinal VEGFR-2 promoter activity and NF-κB activity profiles, as respective agents of angiogenesis and inflammation, during LBD healing. The extended inflammation phase and eventually more rapid resorption of scaffold caused by the addition of strontium accelerates temporary bridging of the fracture gaps. This finding has the potential to inform an improved treatment strategy for patients who suffer from osteoporosis. MDPI 2020-05-01 /pmc/articles/PMC7246816/ /pubmed/32370039 http://dx.doi.org/10.3390/ijms21093208 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Tohidnezhad, Mersedeh Kubo, Yusuke Lichte, Philipp Heigl, Tobias Roch, Diana Barahmand Pour, Nazanin Bergmann, Christian Sönmez, Tolga Taha Hock, Jennifer Vanessa Phi Fragoulis, Athanassios Gremse, Felix Rosenhain, Stefanie Slowik, Alexander Bienert, Michaela Kweider, Nisreen Wruck, Christoph Jan Jahr, Holger Hildebrand, Frank Pape, Hans Christoph Neuß, Sabine Fischer, Horst Pufe, Thomas Effects of Strontium-Doped β-Tricalcium Scaffold on Longitudinal Nuclear Factor-Kappa Beta and Vascular Endothelial Growth Factor Receptor-2 Promoter Activities during Healing in a Murine Critical-Size Bone Defect Model |
title | Effects of Strontium-Doped β-Tricalcium Scaffold on Longitudinal Nuclear Factor-Kappa Beta and Vascular Endothelial Growth Factor Receptor-2 Promoter Activities during Healing in a Murine Critical-Size Bone Defect Model |
title_full | Effects of Strontium-Doped β-Tricalcium Scaffold on Longitudinal Nuclear Factor-Kappa Beta and Vascular Endothelial Growth Factor Receptor-2 Promoter Activities during Healing in a Murine Critical-Size Bone Defect Model |
title_fullStr | Effects of Strontium-Doped β-Tricalcium Scaffold on Longitudinal Nuclear Factor-Kappa Beta and Vascular Endothelial Growth Factor Receptor-2 Promoter Activities during Healing in a Murine Critical-Size Bone Defect Model |
title_full_unstemmed | Effects of Strontium-Doped β-Tricalcium Scaffold on Longitudinal Nuclear Factor-Kappa Beta and Vascular Endothelial Growth Factor Receptor-2 Promoter Activities during Healing in a Murine Critical-Size Bone Defect Model |
title_short | Effects of Strontium-Doped β-Tricalcium Scaffold on Longitudinal Nuclear Factor-Kappa Beta and Vascular Endothelial Growth Factor Receptor-2 Promoter Activities during Healing in a Murine Critical-Size Bone Defect Model |
title_sort | effects of strontium-doped β-tricalcium scaffold on longitudinal nuclear factor-kappa beta and vascular endothelial growth factor receptor-2 promoter activities during healing in a murine critical-size bone defect model |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246816/ https://www.ncbi.nlm.nih.gov/pubmed/32370039 http://dx.doi.org/10.3390/ijms21093208 |
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