Related Experiment Video
Updated: Jun 17, 2026

Isolation of Primary Myofibroblasts from Mouse and Human Colon Tissue
Published on: October 12, 2013
The effect of the pro-inflammatory cytokine tumor necrosis factor-alpha on human joint capsule myofibroblasts
Stefan G Mattyasovszky1, Alexander Hofmann, Christoph Brochhausen
1Department of Trauma and Orthopaedic Surgery, Johannes Gutenberg University School of Medicine, Langenbeckstr, 1, 55101 Mainz, Germany. Stefan.Mattyasovszky@gmx.de
Introduction:
Previous studies have shown that the number of myoblastically differentiated fibroblasts known as myofibroblasts (MFs) is significantly increased in stiff joint capsules, indicating their crucial role in the pathogenesis of post-traumatic joint stiffness. Although the mode of MFs' function has been well defined for different diseases associated with tissue fibrosis, the underlying mechanisms of their regulation in the pathogenesis of post-traumatic joint capsule contracture are largely unknown.
Methods:
In this study, we examined the impact of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) on cellular functions of human joint capsule MFs. MFs were challenged with different concentrations of TNF-alpha with or without both its specifically inactivating antibody infliximab (IFX) and cyclooxygenase-2 (COX2) inhibitor diclofenac. Cell proliferation, gene expression of both alpha-smooth muscle actin (alpha-SMA) and collagen type I, the synthesis of prostaglandin derivates E2, F1A, and F2A, as well as the ability to contract the extracellular matrix were assayed in monolayers and in a three-dimensional collagen gel contraction model. The alpha-SMA and COX2 protein expressions were evaluated by immunofluorescence staining and Western blot analysis.
Results:
The results indicate that TNF-alpha promotes cell viability and proliferation of MFs, but significantly inhibits the contraction of the extracellular matrix in a dose-dependent manner. This effect was associated with downregulation of alpha-SMA and collagen type I by TNF-alpha application. Furthermore, we found a significant time-dependent upregulation of prostaglandin E2 synthesis upon TNF-alpha treatment. The effect of TNF-alpha on COX2-positive MFs could be specifically prevented by IFX and partially reduced by the COX2 inhibitor diclofenac.
Conclusions:
Our results provide evidence that TNF-alpha specifically modulates the function of MFs through regulation of prostaglandin E2 synthesis and therefore may play a crucial role in the pathogenesis of joint capsule contractures.
Related Concept Videos
TGF - β Signaling Pathway
T Cell Types and Functions
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Inflammatory Response II: Inflammatory Exudate and Tissue Repair
The typical wound exudate is odorless, transparent, straw-colored, thin, and watery. Exudate, however, can differ depending on the state of wound healing. Likewise, the exudate's...
Chronic Inflammation: Introduction
NF-κB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
Inflammatory Response
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
