Alterations in macrophage polarization in the craniofacial and extracranial skeleton after zoledronate application and surgical interventions – an in vivo experiment
PurposeMedication-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 tha...
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| Format: | Article |
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Frontiers Media S.A.
2023-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1204188/full |
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| author | Ann-Kristin Struckmeier Ann-Kristin Struckmeier Ann-Kristin Struckmeier Falk Wehrhan Falk Wehrhan Falk Wehrhan Raimund Preidl Raimund Preidl Raimund Preidl Melanie Mike Melanie Mike Melanie Mike Tina Mönch Tina Mönch Tina Mönch Lea Eilers Lea Eilers Lea Eilers Jutta Ries Jutta Ries Jutta Ries Leah Trumet Leah Trumet Leah Trumet Leah Trumet Rainer Lutz Rainer Lutz Rainer Lutz Carol Geppert Marco Kesting Marco Kesting Marco Kesting Manuel Weber Manuel Weber Manuel Weber |
| author_facet | Ann-Kristin Struckmeier Ann-Kristin Struckmeier Ann-Kristin Struckmeier Falk Wehrhan Falk Wehrhan Falk Wehrhan Raimund Preidl Raimund Preidl Raimund Preidl Melanie Mike Melanie Mike Melanie Mike Tina Mönch Tina Mönch Tina Mönch Lea Eilers Lea Eilers Lea Eilers Jutta Ries Jutta Ries Jutta Ries Leah Trumet Leah Trumet Leah Trumet Leah Trumet Rainer Lutz Rainer Lutz Rainer Lutz Carol Geppert Marco Kesting Marco Kesting Marco Kesting Manuel Weber Manuel Weber Manuel Weber |
| author_sort | Ann-Kristin Struckmeier |
| collection | DOAJ |
| description | PurposeMedication-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 methodsAn 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.ResultsComparing 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.ConclusionOur 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. |
| first_indexed | 2024-03-13T09:53:49Z |
| format | Article |
| id | doaj.art-b1fe6c4aa03c48fdb4d50ae5f2d3c8cc |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-13T09:53:49Z |
| publishDate | 2023-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-b1fe6c4aa03c48fdb4d50ae5f2d3c8cc2023-05-24T05:27:46ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-05-011410.3389/fimmu.2023.12041881204188Alterations in macrophage polarization in the craniofacial and extracranial skeleton after zoledronate application and surgical interventions – an in vivo experimentAnn-Kristin Struckmeier0Ann-Kristin Struckmeier1Ann-Kristin Struckmeier2Falk Wehrhan3Falk Wehrhan4Falk Wehrhan5Raimund Preidl6Raimund Preidl7Raimund Preidl8Melanie Mike9Melanie Mike10Melanie Mike11Tina Mönch12Tina Mönch13Tina Mönch14Lea Eilers15Lea Eilers16Lea Eilers17Jutta Ries18Jutta Ries19Jutta Ries20Leah Trumet21Leah Trumet22Leah Trumet23Leah Trumet24Rainer Lutz25Rainer Lutz26Rainer Lutz27Carol Geppert28Marco Kesting29Marco Kesting30Marco Kesting31Manuel Weber32Manuel Weber33Manuel Weber34Department of Oral and Cranio-Maxillofacial Surgery, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, GermanyComprehensive Cancer Center Erlangen-European Metropolitan Area of Nürnberg (CCC ER-EMN), Erlangen, GermanyDeutsches Zentrum Immuntherapie (DZI), Erlangen, GermanyDepartment of Oral and Cranio-Maxillofacial Surgery, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, GermanyComprehensive Cancer Center Erlangen-European Metropolitan Area of Nürnberg (CCC ER-EMN), Erlangen, GermanyDeutsches Zentrum Immuntherapie (DZI), Erlangen, GermanyDepartment of Oral and Cranio-Maxillofacial Surgery, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, GermanyComprehensive Cancer Center Erlangen-European Metropolitan Area of Nürnberg (CCC ER-EMN), Erlangen, GermanyDeutsches Zentrum Immuntherapie (DZI), Erlangen, GermanyDepartment of Oral and Cranio-Maxillofacial Surgery, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, GermanyComprehensive Cancer Center Erlangen-European Metropolitan Area of Nürnberg (CCC ER-EMN), Erlangen, GermanyDeutsches Zentrum Immuntherapie (DZI), Erlangen, GermanyDepartment of Oral and Cranio-Maxillofacial Surgery, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, GermanyComprehensive Cancer Center Erlangen-European Metropolitan Area of Nürnberg (CCC ER-EMN), Erlangen, GermanyDeutsches Zentrum Immuntherapie (DZI), Erlangen, GermanyDepartment of Oral and Cranio-Maxillofacial Surgery, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, GermanyComprehensive Cancer Center Erlangen-European Metropolitan Area of Nürnberg (CCC ER-EMN), Erlangen, GermanyDeutsches Zentrum Immuntherapie (DZI), Erlangen, GermanyDepartment of Oral and Cranio-Maxillofacial Surgery, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, GermanyComprehensive Cancer Center Erlangen-European Metropolitan Area of Nürnberg (CCC ER-EMN), Erlangen, GermanyDeutsches Zentrum Immuntherapie (DZI), Erlangen, GermanyDepartment of Oral and Cranio-Maxillofacial Surgery, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, GermanyComprehensive Cancer Center Erlangen-European Metropolitan Area of Nürnberg (CCC ER-EMN), Erlangen, GermanyDeutsches Zentrum Immuntherapie (DZI), Erlangen, GermanyDepartment of Operative Dentistry and Periodontology, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, GermanyDepartment of Oral and Cranio-Maxillofacial Surgery, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, GermanyComprehensive Cancer Center Erlangen-European Metropolitan Area of Nürnberg (CCC ER-EMN), Erlangen, GermanyDeutsches Zentrum Immuntherapie (DZI), Erlangen, GermanyInstitute of Pathology, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Erlangen, GermanyDepartment of Oral and Cranio-Maxillofacial Surgery, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, GermanyComprehensive Cancer Center Erlangen-European Metropolitan Area of Nürnberg (CCC ER-EMN), Erlangen, GermanyDeutsches Zentrum Immuntherapie (DZI), Erlangen, GermanyDepartment of Oral and Cranio-Maxillofacial Surgery, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, GermanyComprehensive Cancer Center Erlangen-European Metropolitan Area of Nürnberg (CCC ER-EMN), Erlangen, GermanyDeutsches Zentrum Immuntherapie (DZI), Erlangen, GermanyPurposeMedication-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 methodsAn 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.ResultsComparing 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.ConclusionOur 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.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1204188/fullosteonecrosisbisphosphonatemacrophagetooth extractionMRONJ |
| spellingShingle | Ann-Kristin Struckmeier Ann-Kristin Struckmeier Ann-Kristin Struckmeier Falk Wehrhan Falk Wehrhan Falk Wehrhan Raimund Preidl Raimund Preidl Raimund Preidl Melanie Mike Melanie Mike Melanie Mike Tina Mönch Tina Mönch Tina Mönch Lea Eilers Lea Eilers Lea Eilers Jutta Ries Jutta Ries Jutta Ries Leah Trumet Leah Trumet Leah Trumet Leah Trumet Rainer Lutz Rainer Lutz Rainer Lutz Carol Geppert Marco Kesting Marco Kesting Marco Kesting Manuel Weber Manuel Weber Manuel Weber Alterations in macrophage polarization in the craniofacial and extracranial skeleton after zoledronate application and surgical interventions – an in vivo experiment Frontiers in Immunology osteonecrosis bisphosphonate macrophage tooth extraction MRONJ |
| 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 | osteonecrosis bisphosphonate macrophage tooth extraction MRONJ |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1204188/full |
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