Cargando…

Alterations in macrophage polarization in the craniofacial and extracranial skeleton after zoledronate application and surgical interventions – an in vivo experiment

PURPOSE: Medication-related osteonecrosis occurs exclusively in the jaw bones. However, the exact pathogenesis of medication-related osteonecrosis of the jaw (MRONJ) and the unique predisposition of the jaw bones have not been elucidated, making its treatment a challenge. Recent evidence indicates t...

Descripción completa

Detalles Bibliográficos
Autores principales: Struckmeier, Ann-Kristin, Wehrhan, Falk, Preidl, Raimund, Mike, Melanie, Mönch, Tina, Eilers, Lea, Ries, Jutta, Trumet, Leah, Lutz, Rainer, Geppert, Carol, Kesting, Marco, Weber, Manuel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10244663/
https://www.ncbi.nlm.nih.gov/pubmed/37292209
http://dx.doi.org/10.3389/fimmu.2023.1204188
_version_ 1785054690972532736
author Struckmeier, Ann-Kristin
Wehrhan, Falk
Preidl, Raimund
Mike, Melanie
Mönch, Tina
Eilers, Lea
Ries, Jutta
Trumet, Leah
Lutz, Rainer
Geppert, Carol
Kesting, Marco
Weber, Manuel
author_facet Struckmeier, Ann-Kristin
Wehrhan, Falk
Preidl, Raimund
Mike, Melanie
Mönch, Tina
Eilers, Lea
Ries, Jutta
Trumet, Leah
Lutz, Rainer
Geppert, Carol
Kesting, Marco
Weber, Manuel
author_sort Struckmeier, Ann-Kristin
collection PubMed
description PURPOSE: Medication-related osteonecrosis occurs exclusively in the jaw bones. However, the exact pathogenesis of medication-related osteonecrosis of the jaw (MRONJ) and the unique predisposition of the jaw bones have not been elucidated, making its treatment a challenge. Recent evidence indicates that macrophages might play a pivotal role in MRONJ pathogenesis. The aim of the present study was to compare the macrophage populations between the craniofacial and extracranial skeleton and to investigate the changes induced by zoledronate (Zol) application and surgical interventions. MATERIALS AND METHODS: An in vivo experiment was performed. 120 wistar rats were randomized to 4 groups (G1, G2, G3, G4). G1 served as an untreated control group. G2 and G4 received Zol injections for 8 weeks. Afterwards, the right lower molar of the animals from G3 and G4 was extracted and the right tibia osteotomized followed by osteosynthesis. Tissue samples were taken from the extraction socket and the tibia fracture at fixed time points. Immunohistochemistry was conducted to determine the labeling indexes of CD68(+) and CD163(+) macrophages. RESULTS: Comparing the mandible and the tibia, we observed a significantly higher number of macrophages and a heightened pro-inflammatory environment in the mandible compared to the tibia. Tooth extraction caused an increase of the overall number of macrophages and a shift toward a more pro-inflammatory microenvironment in the mandible. Zol application amplified this effect. CONCLUSION: Our results indicate fundamental immunological differences between the jaw bone and the tibia, which might be a reason for the unique predisposition for MRONJ in the jaw bones. The more pro-inflammatory environment after Zol application and tooth extraction might contribute to the pathogenesis of MRONJ. Targeting macrophages might represent an attractive strategy to prevent MRONJ and improve therapy. In addition, our results support the hypothesis of an anti-tumoral and anti-metastatic effect induced by BPs. However, further studies are needed to delineate the mechanisms and specify the contributions of the various macrophage phenotypes.
format Online
Article
Text
id pubmed-10244663
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-102446632023-06-08 Alterations in macrophage polarization in the craniofacial and extracranial skeleton after zoledronate application and surgical interventions – an in vivo experiment Struckmeier, Ann-Kristin Wehrhan, Falk Preidl, Raimund Mike, Melanie Mönch, Tina Eilers, Lea Ries, Jutta Trumet, Leah Lutz, Rainer Geppert, Carol Kesting, Marco Weber, Manuel Front Immunol Immunology PURPOSE: Medication-related osteonecrosis occurs exclusively in the jaw bones. However, the exact pathogenesis of medication-related osteonecrosis of the jaw (MRONJ) and the unique predisposition of the jaw bones have not been elucidated, making its treatment a challenge. Recent evidence indicates that macrophages might play a pivotal role in MRONJ pathogenesis. The aim of the present study was to compare the macrophage populations between the craniofacial and extracranial skeleton and to investigate the changes induced by zoledronate (Zol) application and surgical interventions. MATERIALS AND METHODS: An in vivo experiment was performed. 120 wistar rats were randomized to 4 groups (G1, G2, G3, G4). G1 served as an untreated control group. G2 and G4 received Zol injections for 8 weeks. Afterwards, the right lower molar of the animals from G3 and G4 was extracted and the right tibia osteotomized followed by osteosynthesis. Tissue samples were taken from the extraction socket and the tibia fracture at fixed time points. Immunohistochemistry was conducted to determine the labeling indexes of CD68(+) and CD163(+) macrophages. RESULTS: Comparing the mandible and the tibia, we observed a significantly higher number of macrophages and a heightened pro-inflammatory environment in the mandible compared to the tibia. Tooth extraction caused an increase of the overall number of macrophages and a shift toward a more pro-inflammatory microenvironment in the mandible. Zol application amplified this effect. CONCLUSION: Our results indicate fundamental immunological differences between the jaw bone and the tibia, which might be a reason for the unique predisposition for MRONJ in the jaw bones. The more pro-inflammatory environment after Zol application and tooth extraction might contribute to the pathogenesis of MRONJ. Targeting macrophages might represent an attractive strategy to prevent MRONJ and improve therapy. In addition, our results support the hypothesis of an anti-tumoral and anti-metastatic effect induced by BPs. However, further studies are needed to delineate the mechanisms and specify the contributions of the various macrophage phenotypes. Frontiers Media S.A. 2023-05-24 /pmc/articles/PMC10244663/ /pubmed/37292209 http://dx.doi.org/10.3389/fimmu.2023.1204188 Text en Copyright © 2023 Struckmeier, Wehrhan, Preidl, Mike, Mönch, Eilers, Ries, Trumet, Lutz, Geppert, Kesting and Weber https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Struckmeier, Ann-Kristin
Wehrhan, Falk
Preidl, Raimund
Mike, Melanie
Mönch, Tina
Eilers, Lea
Ries, Jutta
Trumet, Leah
Lutz, Rainer
Geppert, Carol
Kesting, Marco
Weber, Manuel
Alterations in macrophage polarization in the craniofacial and extracranial skeleton after zoledronate application and surgical interventions – an in vivo experiment
title Alterations in macrophage polarization in the craniofacial and extracranial skeleton after zoledronate application and surgical interventions – an in vivo experiment
title_full Alterations in macrophage polarization in the craniofacial and extracranial skeleton after zoledronate application and surgical interventions – an in vivo experiment
title_fullStr Alterations in macrophage polarization in the craniofacial and extracranial skeleton after zoledronate application and surgical interventions – an in vivo experiment
title_full_unstemmed Alterations in macrophage polarization in the craniofacial and extracranial skeleton after zoledronate application and surgical interventions – an in vivo experiment
title_short Alterations in macrophage polarization in the craniofacial and extracranial skeleton after zoledronate application and surgical interventions – an in vivo experiment
title_sort alterations in macrophage polarization in the craniofacial and extracranial skeleton after zoledronate application and surgical interventions – an in vivo experiment
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10244663/
https://www.ncbi.nlm.nih.gov/pubmed/37292209
http://dx.doi.org/10.3389/fimmu.2023.1204188
work_keys_str_mv AT struckmeierannkristin alterationsinmacrophagepolarizationinthecraniofacialandextracranialskeletonafterzoledronateapplicationandsurgicalinterventionsaninvivoexperiment
AT wehrhanfalk alterationsinmacrophagepolarizationinthecraniofacialandextracranialskeletonafterzoledronateapplicationandsurgicalinterventionsaninvivoexperiment
AT preidlraimund alterationsinmacrophagepolarizationinthecraniofacialandextracranialskeletonafterzoledronateapplicationandsurgicalinterventionsaninvivoexperiment
AT mikemelanie alterationsinmacrophagepolarizationinthecraniofacialandextracranialskeletonafterzoledronateapplicationandsurgicalinterventionsaninvivoexperiment
AT monchtina alterationsinmacrophagepolarizationinthecraniofacialandextracranialskeletonafterzoledronateapplicationandsurgicalinterventionsaninvivoexperiment
AT eilerslea alterationsinmacrophagepolarizationinthecraniofacialandextracranialskeletonafterzoledronateapplicationandsurgicalinterventionsaninvivoexperiment
AT riesjutta alterationsinmacrophagepolarizationinthecraniofacialandextracranialskeletonafterzoledronateapplicationandsurgicalinterventionsaninvivoexperiment
AT trumetleah alterationsinmacrophagepolarizationinthecraniofacialandextracranialskeletonafterzoledronateapplicationandsurgicalinterventionsaninvivoexperiment
AT lutzrainer alterationsinmacrophagepolarizationinthecraniofacialandextracranialskeletonafterzoledronateapplicationandsurgicalinterventionsaninvivoexperiment
AT geppertcarol alterationsinmacrophagepolarizationinthecraniofacialandextracranialskeletonafterzoledronateapplicationandsurgicalinterventionsaninvivoexperiment
AT kestingmarco alterationsinmacrophagepolarizationinthecraniofacialandextracranialskeletonafterzoledronateapplicationandsurgicalinterventionsaninvivoexperiment
AT webermanuel alterationsinmacrophagepolarizationinthecraniofacialandextracranialskeletonafterzoledronateapplicationandsurgicalinterventionsaninvivoexperiment