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Gene Expression Profiling of Peri-Implant Healing of PLGA-Li(+) Implants Suggests an Activated Wnt Signaling Pathway In Vivo

Bone development and regeneration is associated with the Wnt signaling pathway that, according to literature, can be modulated by lithium ions (Li(+)). The aim of this study was to evaluate the gene expression profile during peri-implant healing of poly(lactic-co-glycolic acid) (PLGA) implants with...

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Autores principales: Thorfve, Anna, Bergstrand, Anna, Ekström, Karin, Lindahl, Anders, Thomsen, Peter, Larsson, Anette, Tengvall, Pentti
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4105622/
https://www.ncbi.nlm.nih.gov/pubmed/25047349
http://dx.doi.org/10.1371/journal.pone.0102597
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author Thorfve, Anna
Bergstrand, Anna
Ekström, Karin
Lindahl, Anders
Thomsen, Peter
Larsson, Anette
Tengvall, Pentti
author_facet Thorfve, Anna
Bergstrand, Anna
Ekström, Karin
Lindahl, Anders
Thomsen, Peter
Larsson, Anette
Tengvall, Pentti
author_sort Thorfve, Anna
collection PubMed
description Bone development and regeneration is associated with the Wnt signaling pathway that, according to literature, can be modulated by lithium ions (Li(+)). The aim of this study was to evaluate the gene expression profile during peri-implant healing of poly(lactic-co-glycolic acid) (PLGA) implants with incorporated Li(+), while PLGA without Li(+) was used as control, and a special attention was then paid to the Wnt signaling pathway. The implants were inserted in rat tibia for 7 or 28 days and the gene expression profile was investigated using a genome-wide microarray analysis. The results were verified by qPCR and immunohistochemistry. Histomorphometry was used to evaluate the possible effect of Li(+) on bone regeneration. The microarray analysis revealed a large number of significantly differentially regulated genes over time within the two implant groups. The Wnt signaling pathway was significantly affected by Li(+), with approximately 34% of all Wnt-related markers regulated over time, compared to 22% for non-Li(+) containing (control; Ctrl) implants. Functional cluster analysis indicated skeletal system morphogenesis, cartilage development and condensation as related to Li(+). The downstream Wnt target gene, FOSL1, and the extracellular protein-encoding gene, ASPN, were significantly upregulated by Li(+) compared with Ctrl. The presence of β-catenin, FOSL1 and ASPN positive cells was confirmed around implants of both groups. Interestingly, a significantly reduced bone area was observed over time around both implant groups. The presence of periostin and calcitonin receptor-positive cells was observed at both time points. This study is to the best of the authors' knowledge the first report evaluating the effect of a local release of Li(+) from PLGA at the fracture site. The present study shows that during the current time frame and with the present dose of Li(+) in PLGA implants, Li(+) is not an enhancer of early bone growth, although it affects the Wnt signaling pathway.
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spelling pubmed-41056222014-07-23 Gene Expression Profiling of Peri-Implant Healing of PLGA-Li(+) Implants Suggests an Activated Wnt Signaling Pathway In Vivo Thorfve, Anna Bergstrand, Anna Ekström, Karin Lindahl, Anders Thomsen, Peter Larsson, Anette Tengvall, Pentti PLoS One Research Article Bone development and regeneration is associated with the Wnt signaling pathway that, according to literature, can be modulated by lithium ions (Li(+)). The aim of this study was to evaluate the gene expression profile during peri-implant healing of poly(lactic-co-glycolic acid) (PLGA) implants with incorporated Li(+), while PLGA without Li(+) was used as control, and a special attention was then paid to the Wnt signaling pathway. The implants were inserted in rat tibia for 7 or 28 days and the gene expression profile was investigated using a genome-wide microarray analysis. The results were verified by qPCR and immunohistochemistry. Histomorphometry was used to evaluate the possible effect of Li(+) on bone regeneration. The microarray analysis revealed a large number of significantly differentially regulated genes over time within the two implant groups. The Wnt signaling pathway was significantly affected by Li(+), with approximately 34% of all Wnt-related markers regulated over time, compared to 22% for non-Li(+) containing (control; Ctrl) implants. Functional cluster analysis indicated skeletal system morphogenesis, cartilage development and condensation as related to Li(+). The downstream Wnt target gene, FOSL1, and the extracellular protein-encoding gene, ASPN, were significantly upregulated by Li(+) compared with Ctrl. The presence of β-catenin, FOSL1 and ASPN positive cells was confirmed around implants of both groups. Interestingly, a significantly reduced bone area was observed over time around both implant groups. The presence of periostin and calcitonin receptor-positive cells was observed at both time points. This study is to the best of the authors' knowledge the first report evaluating the effect of a local release of Li(+) from PLGA at the fracture site. The present study shows that during the current time frame and with the present dose of Li(+) in PLGA implants, Li(+) is not an enhancer of early bone growth, although it affects the Wnt signaling pathway. Public Library of Science 2014-07-21 /pmc/articles/PMC4105622/ /pubmed/25047349 http://dx.doi.org/10.1371/journal.pone.0102597 Text en © 2014 Thorfve 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
Thorfve, Anna
Bergstrand, Anna
Ekström, Karin
Lindahl, Anders
Thomsen, Peter
Larsson, Anette
Tengvall, Pentti
Gene Expression Profiling of Peri-Implant Healing of PLGA-Li(+) Implants Suggests an Activated Wnt Signaling Pathway In Vivo
title Gene Expression Profiling of Peri-Implant Healing of PLGA-Li(+) Implants Suggests an Activated Wnt Signaling Pathway In Vivo
title_full Gene Expression Profiling of Peri-Implant Healing of PLGA-Li(+) Implants Suggests an Activated Wnt Signaling Pathway In Vivo
title_fullStr Gene Expression Profiling of Peri-Implant Healing of PLGA-Li(+) Implants Suggests an Activated Wnt Signaling Pathway In Vivo
title_full_unstemmed Gene Expression Profiling of Peri-Implant Healing of PLGA-Li(+) Implants Suggests an Activated Wnt Signaling Pathway In Vivo
title_short Gene Expression Profiling of Peri-Implant Healing of PLGA-Li(+) Implants Suggests an Activated Wnt Signaling Pathway In Vivo
title_sort gene expression profiling of peri-implant healing of plga-li(+) implants suggests an activated wnt signaling pathway in vivo
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4105622/
https://www.ncbi.nlm.nih.gov/pubmed/25047349
http://dx.doi.org/10.1371/journal.pone.0102597
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