Journal Article

The effect of Rsk2 on TNFα-mediated bone loss in the TMJ and craniofacial skeleton

Heimel, Patrick, Kahl-Nieke, Bärbel, Amling, Michael, Tangl, Stefan, Schett, Georg, Bachmann, Frédéric, Petersen, Julian, Gruber, Reinhard, Schinke, Thorsten, Luther, Julia, Derer, Anja, Koehne, Till, Hirsch, Christian, LeBlanc, Aaron, Helms, Jill, Georgi, Gina Marie

2025

Overview

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.

• Publisher: BioMed Central,Springer Nature B.V,BMC
• Subject: Animals / Apoptosis / Appendicular skeleton / Bone loss / Bone resorption / Bone Resorption - metabolism / Bones / Cartilage / Clinical trials / Computed tomography / Cytokines / Dentistry / Dimensional analysis / Geometric morphometrics / Homeostasis / Inflammation / Integrated software / Kinases / Laboratory animals / Long bone / Mandible / Mandible - pathology / Medicine / Mice / Mice, Inbred C57BL / Mice, Knockout / Oral and Maxillofacial Surgery / Pathogenesis / Rheumatoid arthritis / Ribosomal protein S6 kinase / Ribosomal Protein S6 Kinases, 90-kDa - genetics / Ribosomal Protein S6 Kinases, 90-kDa - metabolism / Ribosomal Protein S6 Kinases, 90-kDa - physiology / Skeleton / Skull / Skull - diagnostic imaging / Skull - pathology / Synovial membrane / Temporomandibular joint / Temporomandibular Joint - diagnostic imaging / Temporomandibular Joint - pathology / Temporomandibular Joint Disorders / Temporomandibular joints / Therapeutic applications / Transgenic mouse / Tumor Necrosis Factor-alpha - metabolism / Tumor necrosis factor-TNF / Tumor necrosis factor-α / Tumor necrosis factor-α, ribosomal s6 kinase 2 / X-Ray Microtomography