Related Experiment Video

Updated: Aug 5, 2026

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity
07:09

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity

Published on: January 7, 2019

IL-1- and TNF-induced bone resorption is mediated by p38 mitogen activated protein kinase

S Kumar1, B J Votta, D J Rieman

  • 1Department of Musculoskeletal Diseases, Glaxo SmithKline, King of Prussia, Pennsylvania, USA. Sanjay_Kumar@SBPHRD.COM

Journal of Cellular Physiology
|April 25, 2001
PubMed

Insights

p38 mitogen-activated protein kinase (MAPK) inhibitors effectively block inflammatory cytokines like TNF and IL-1, crucial for bone and cartilage health. Targeting this pathway shows therapeutic potential for joint diseases like rheumatoid arthritis.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Pharmacology

Background:

  • p38 mitogen-activated protein kinase (MAPK) signaling is implicated in inflammatory processes.
  • Previous studies indicated p38 MAPK inhibitors are effective in models of bone and cartilage degradation.

Purpose of the Study:

  • To investigate the role and activation of p38 MAPK in osteoblasts and chondrocytes.
  • To evaluate the therapeutic potential of p38 MAPK inhibitors in inflammatory bone and cartilage diseases.

Main Methods:

  • Treatment of osteoblasts and chondrocytes with pro-inflammatory and osteotropic agents.
  • Assay of p38 MAPK activation and IL-6 production.
  • Inhibition studies using SB 203580, a selective p38 MAPK inhibitor.
  • Assessment of p38 MAPK activation and bone resorption in fetal rat long bones.

Main Results:

  • IL-1 and TNF significantly activated p38 MAPK in osteoblasts and chondrocytes, but not other tested agents.
  • SB 203580 inhibited IL-1 and TNF-induced p38 MAPK activity and IL-6 production.
  • IL-1 and TNF activated p38 MAPK in fetal rat long bones, and inhibitors reduced bone resorption.

Conclusions:

  • p38 MAPK plays a central role in regulating inflammatory cytokine production and response in bone and cartilage.
  • Selective inhibition of the p38 MAPK pathway demonstrates therapeutic potential for joint diseases such as rheumatoid arthritis (RA).

More Related Videos

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

A Simple Pit Assay Protocol to Visualize and Quantify Osteoclastic Resorption In Vitro07:03

A Simple Pit Assay Protocol to Visualize and Quantify Osteoclastic Resorption In Vitro

Published on: June 16, 2022

Related Concept Videos

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 heterodimer of NF-κB...
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 bone...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
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...
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 are of three kinds RI, RII, and RIII. The RI...
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...