The effect of Rsk2 on TNFα-mediated bone loss in the TMJ and craniofacial skeleton
Abstract Objectives This study aims to investigate the impact of the pro-osteoblastogenic ERK-activated ribosomal S6 kinase (Rsk2) on Tumor necrosis factor (TNF)α-induced bone loss in the craniofacial system, focusing on its role in rheumatoid arthritis (RA). The objective is to understand whether R...
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BMC
2025-03-01
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| Series: | BMC Oral Health |
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| Online Access: | https://doi.org/10.1186/s12903-025-05779-9 |
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| author | Gina Marie Georgi Frédéric Bachmann Julia Luther Anja Derer Patrick Heimel Stefan Tangl Bärbel Kahl-Nieke Aaron LeBlanc Jill Helms Georg Schett Christian Hirsch Reinhard Gruber Michael Amling Thorsten Schinke Till Koehne Julian Petersen |
| author_facet | Gina Marie Georgi Frédéric Bachmann Julia Luther Anja Derer Patrick Heimel Stefan Tangl Bärbel Kahl-Nieke Aaron LeBlanc Jill Helms Georg Schett Christian Hirsch Reinhard Gruber Michael Amling Thorsten Schinke Till Koehne Julian Petersen |
| author_sort | Gina Marie Georgi |
| collection | DOAJ |
| description | Abstract Objectives This study aims to investigate the impact of the pro-osteoblastogenic ERK-activated ribosomal S6 kinase (Rsk2) on Tumor necrosis factor (TNF)α-induced bone loss in the craniofacial system, focusing on its role in rheumatoid arthritis (RA). The objective is to understand whether Rsk2, previously shown to have protective effects in long bones against TNFα-induced bone resorption, exhibits similar effects in the craniofacial region. Materials , and Methods. The study compares mice with TNFα overexpression, Rsk2 knockout mice, and a combination of TNFα, and Rsk2 knockout mice using detailed micro-computed tomography coupled with landmark based morphometric analysis, and classical histology. The overall skull morphology, mandible shape, and the temporomandibular joint were examined. Additionally, histological sections were utilized to examine the synovial membrane. Results Combining TNFα, and Rsk2 deficiency does not further alter overall skull shape compared to TNFα alone. TNFα overexpression shortens the mandibular ramus, exacerbated by Rsk2 absence. Micro-computed tomography (µCT) reveals significant temporomandibular joint damage from TNFα, independent of Rsk2. However, histological sections show increased synovial membrane thickness with TNFα, heightened in the absence of Rsk2. Conclusions Rsk2 mitigates TNFα-induced effects on mandibular ramus length in the craniofacial system but has limited impact on the temporomandibular joint, except for synovial membrane thickness. Overall, Rsk2 demonstrates a weaker preventive effect on TNFα-induced craniofacial bone loss compared to its established role in the appendicular skeleton. Clinical Relevance This study highlights regional differences in Rsk2's protective mechanisms, emphasizing the need for further exploration of the underlying mechanisms for these disparities. Understanding these regional differences can be crucial for the development of targeted therapeutic interventions. |
| format | Article |
| id | doaj-art-2adeaaea09a84d6dac20fdc4e5ef8d13 |
| institution | DOAJ |
| issn | 1472-6831 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Oral Health |
| spelling | doaj-art-2adeaaea09a84d6dac20fdc4e5ef8d132025-08-20T02:49:12ZengBMCBMC Oral Health1472-68312025-03-0125111110.1186/s12903-025-05779-9The effect of Rsk2 on TNFα-mediated bone loss in the TMJ and craniofacial skeletonGina Marie Georgi0Frédéric Bachmann1Julia Luther2Anja Derer3Patrick Heimel4Stefan Tangl5Bärbel Kahl-Nieke6Aaron LeBlanc7Jill Helms8Georg Schett9Christian Hirsch10Reinhard Gruber11Michael Amling12Thorsten Schinke13Till Koehne14Julian Petersen15Department of Orthodontics, University of Leipzig Medical CenterDepartment of Orthodontics, University Medical Center Hamburg-EppendorfInstitute of Osteology, and Biomechanics, University Medical Center Hamburg-EppendorfDepartment of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU)Department of Oral Surgery, University Clinic of Dentistry, Medical University of ViennaDepartment of Oral Surgery, University Clinic of Dentistry, Medical University of ViennaDepartment of Orthodontics, University Medical Center Hamburg-EppendorfCentre for Oral, Clinical & Translational Sciences, Faculty of Dentistry, Oral & Craniofacial Sciences, King’s College LondonDepartment of Surgery, Stanford University School of MedicineDeutsches Zentrum Für Immuntherapie (DZI), Friedrich Alexander University Erlangen-Nuremberg, and Universitätsklinikum ErlangenClinic of Pediatric and Preventive Dentistry, University of LeipzigDepartment of Oral Biology, University Clinic of Dentistry, Medical University of ViennaInstitute of Osteology, and Biomechanics, University Medical Center Hamburg-EppendorfInstitute of Osteology, and Biomechanics, University Medical Center Hamburg-EppendorfDepartment of Orthodontics, University of Leipzig Medical CenterDepartment of Orthodontics, University of Leipzig Medical CenterAbstract Objectives This study aims to investigate the impact of the pro-osteoblastogenic ERK-activated ribosomal S6 kinase (Rsk2) on Tumor necrosis factor (TNF)α-induced bone loss in the craniofacial system, focusing on its role in rheumatoid arthritis (RA). The objective is to understand whether Rsk2, previously shown to have protective effects in long bones against TNFα-induced bone resorption, exhibits similar effects in the craniofacial region. Materials , and Methods. The study compares mice with TNFα overexpression, Rsk2 knockout mice, and a combination of TNFα, and Rsk2 knockout mice using detailed micro-computed tomography coupled with landmark based morphometric analysis, and classical histology. The overall skull morphology, mandible shape, and the temporomandibular joint were examined. Additionally, histological sections were utilized to examine the synovial membrane. Results Combining TNFα, and Rsk2 deficiency does not further alter overall skull shape compared to TNFα alone. TNFα overexpression shortens the mandibular ramus, exacerbated by Rsk2 absence. Micro-computed tomography (µCT) reveals significant temporomandibular joint damage from TNFα, independent of Rsk2. However, histological sections show increased synovial membrane thickness with TNFα, heightened in the absence of Rsk2. Conclusions Rsk2 mitigates TNFα-induced effects on mandibular ramus length in the craniofacial system but has limited impact on the temporomandibular joint, except for synovial membrane thickness. Overall, Rsk2 demonstrates a weaker preventive effect on TNFα-induced craniofacial bone loss compared to its established role in the appendicular skeleton. Clinical Relevance This study highlights regional differences in Rsk2's protective mechanisms, emphasizing the need for further exploration of the underlying mechanisms for these disparities. Understanding these regional differences can be crucial for the development of targeted therapeutic interventions.https://doi.org/10.1186/s12903-025-05779-9Geometric morphometricsInflammationRheumatoid arthritisTransgenic mouseTemporomandibular jointsTumor necrosis factor-α, ribosomal s6 kinase 2 |
| spellingShingle | Gina Marie Georgi Frédéric Bachmann Julia Luther Anja Derer Patrick Heimel Stefan Tangl Bärbel Kahl-Nieke Aaron LeBlanc Jill Helms Georg Schett Christian Hirsch Reinhard Gruber Michael Amling Thorsten Schinke Till Koehne Julian Petersen The effect of Rsk2 on TNFα-mediated bone loss in the TMJ and craniofacial skeleton BMC Oral Health Geometric morphometrics Inflammation Rheumatoid arthritis Transgenic mouse Temporomandibular joints Tumor necrosis factor-α, ribosomal s6 kinase 2 |
| title | The effect of Rsk2 on TNFα-mediated bone loss in the TMJ and craniofacial skeleton |
| title_full | The effect of Rsk2 on TNFα-mediated bone loss in the TMJ and craniofacial skeleton |
| title_fullStr | The effect of Rsk2 on TNFα-mediated bone loss in the TMJ and craniofacial skeleton |
| title_full_unstemmed | The effect of Rsk2 on TNFα-mediated bone loss in the TMJ and craniofacial skeleton |
| title_short | The effect of Rsk2 on TNFα-mediated bone loss in the TMJ and craniofacial skeleton |
| title_sort | effect of rsk2 on tnfα mediated bone loss in the tmj and craniofacial skeleton |
| topic | Geometric morphometrics Inflammation Rheumatoid arthritis Transgenic mouse Temporomandibular joints Tumor necrosis factor-α, ribosomal s6 kinase 2 |
| url | https://doi.org/10.1186/s12903-025-05779-9 |
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