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

Struckmeier AK, Wehrhan F, Preidl R, Mike M, Mönch T, Eilers L, Ries J, Trumet L, Lutz R, Geppert CI, Kesting MR, Weber M (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Frontiers in Immunology Frontiers Research Foundation / Frontiers Media

Book Volume: 14

Article Number: 1204188

DOI: 10.3389/fimmu.2023.1204188

Abstract

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.

Authors with CRIS profile

Ann-Kristin Struckmeier Department of Oral and Cranio-Maxillofacial Surgery Falk Wehrhan Department of Oral and Cranio-Maxillofacial Surgery Raimund Preidl Department of Oral and Cranio-Maxillofacial Surgery Melanie Mike Department of Oral and Cranio-Maxillofacial Surgery Tina Mönch Department of Oral and Cranio-Maxillofacial Surgery Lea Eilers Department of Oral and Cranio-Maxillofacial Surgery Jutta Ries Department of Oral and Cranio-Maxillofacial Surgery Leah Trumet Department of Operative Dentistry and Periodontology Rainer Lutz Department of Oral and Cranio-Maxillofacial Surgery Carol-Immanuel Geppert Institute of Pathology Marco Rainer Kesting Lehrstuhl für Zahnmedizin, insbesondere Mund-, Kiefer-, und Gesichtschirurgie Manuel Weber Department of Oral and Cranio-Maxillofacial Surgery

How to cite

APA:

Struckmeier, A.-K., Wehrhan, F., Preidl, R., Mike, M., Mönch, T., Eilers, L.,... Weber, M. (2023). Alterations in macrophage polarization in the craniofacial and extracranial skeleton after zoledronate application and surgical interventions – an in vivo experiment. Frontiers in Immunology, 14. https://dx.doi.org/10.3389/fimmu.2023.1204188

MLA:

Struckmeier, Ann-Kristin, et al. "Alterations in macrophage polarization in the craniofacial and extracranial skeleton after zoledronate application and surgical interventions – an in vivo experiment." Frontiers in Immunology 14 (2023).

BibTeX: Download