Related Experiment Video

Updated: May 20, 2025

Effect of Anti-c-fms Antibody on Osteoclast Formation and Proliferation of Osteoclast Precursor In Vitro
07:51

Effect of Anti-c-fms Antibody on Osteoclast Formation and Proliferation of Osteoclast Precursor In Vitro

Published on: March 18, 2019

5.9K

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

Gina Marie Georgi1, Frédéric Bachmann2, Julia Luther3

  • 1Department of Orthodontics, University of Leipzig Medical Center​, Liebigstraße 12, 04103, Leipzig, Germany.

BMC Oral Health
|March 27, 2025
PubMed
Abstract

Insights

Ribosomal S6 kinase (Rsk2) offers some protection against Tumor necrosis factor-alpha (TNFα)-induced mandibular bone loss in rheumatoid arthritis models. However, Rsk2 shows limited impact on temporomandibular joint damage, indicating regional differences in its protective role.

Area of Science:

  • Investigates the role of Rsk2 in craniofacial bone metabolism.
  • Examines the impact of TNFα on bone loss in rheumatoid arthritis (RA).
  • Compares Rsk2's function in craniofacial versus appendicular skeletons.

Background:

  • Tumor necrosis factor-alpha (TNFα) is implicated in bone loss associated with rheumatoid arthritis (RA).
  • Ribosomal S6 kinase 2 (Rsk2) has shown protective effects against TNFα-induced bone resorption in long bones.
  • The role of Rsk2 in craniofacial bone, particularly the temporomandibular joint (TMJ), remains less understood.

Purpose of the Study:

  • To determine if Rsk2 protects against TNFα-induced bone loss in the craniofacial system, similar to its role in long bones.
  • To investigate the specific effects of Rsk2 and TNFα on skull morphology, mandible shape, and TMJ in an RA context.

Main Methods:

  • Utilized a comparative mouse model study including TNFα overexpression, Rsk2 knockout, and combined TNFα/Rsk2 knockout mice.
  • Employed micro-computed tomography (µCT) with landmark-based morphometric analysis for detailed skeletal examination.
  • Conducted classical histology to assess TMJ and synovial membrane changes.

Main Results:

  • TNFα overexpression led to mandibular ramus shortening, which was worsened by the absence of Rsk2.
  • Significant temporomandibular joint damage was observed in TNFα-overexpressing mice, irrespective of Rsk2 status.
  • Histological analysis revealed increased synovial membrane thickness in TNFα-treated mice, further elevated in Rsk2 knockout conditions.

Conclusions:

  • Rsk2 partially mitigates TNFα-induced mandibular ramus length reduction but has minimal effect on TMJ structural damage.
  • Rsk2 demonstrates a less pronounced protective effect against craniofacial bone loss compared to its role in the appendicular skeleton.
  • Findings suggest regional variations in Rsk2's protective mechanisms, necessitating further research into underlying molecular pathways for targeted RA therapies.
Keywords:
Geometric morphometricsInflammationRheumatoid arthritisTemporomandibular jointsTransgenic mouseTumor necrosis factor-α, ribosomal s6 kinase 2

More Related Videos

Differentiation of Functional Osteoclasts from Human Peripheral Blood CD14+ Monocytes11:52

Differentiation of Functional Osteoclasts from Human Peripheral Blood CD14+ Monocytes

Published on: January 27, 2023

2.9K
A RANKL-based Osteoclast Culture Assay of Mouse Bone Marrow to Investigate the Role of mTORC1 in Osteoclast Formation09:37

A RANKL-based Osteoclast Culture Assay of Mouse Bone Marrow to Investigate the Role of mTORC1 in Osteoclast Formation

Published on: March 15, 2018

12.9K

Related Concept Videos

The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
8.6K
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.2K
T Cell Types and Functions01:24

T Cell Types and Functions

When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
724
Osteoclasts in Bone Remodeling01:31

Osteoclasts in Bone Remodeling

Osteoclasts are cells responsible for bone resorption and remodeling. They originate from hematopoietic progenitor cells present in the bone marrow. Numerous progenitor cells fuse to form multinucleated cells, each with 10-20 nuclei. A single osteoclast has a diameter of 150 to 200 µM. These cells have ruffled borders that break down the underlying bone tissue and release minerals such as calcium into the blood in bone resorption. Osteoclasts cling to bones with their ruffled edges during...
2.8K
Enzyme-linked Receptors01:00

Enzyme-linked Receptors

Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
76.7K
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
7.2K