Related Experiment Video

Updated: May 1, 2026

Visualization and Quantification of TGFβ/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay
11:38

Visualization and Quantification of TGFβ/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay

Published on: September 14, 2021

2.4K

TNFα, PDGF, and TGFβ synergistically induce synovial lining hyperplasia via inducible PI3Kδ

Hideyuki Shibuya1, Hiroyuki Yoshitomi, Koichi Murata

  • 1Department of Orthopaedic Surgery, Kyoto University Graduate School of Medicine , Kyoto , Japan.

Modern Rheumatology
|April 11, 2014
PubMed
Abstract

Insights

Inducible phosphoinositide 3 kinase delta (PI3Kδ) drives persistent PI3K-Akt pathway activation in fibroblast-like synoviocytes (FLSs). This leads to the formation of a hypertrophic synovial lining, a key feature of rheumatoid arthritis (RA).

Area of Science:

  • Rheumatology
  • Cell Biology
  • Molecular Biology

Background:

  • Rheumatoid arthritis (RA) is characterized by synovial inflammation and hyperplasia.
  • The hypertrophic synovium contributes to joint destruction in RA.
  • Understanding the molecular mechanisms of synovial hypertrophy is crucial for developing targeted therapies.

Purpose of the Study:

  • To elucidate the molecular mechanisms driving synovial hypertrophy in rheumatoid arthritis (RA).
  • To investigate the role of phosphoinositide 3 kinase (PI3K) isoforms in fibroblast-like synoviocyte (FLS) proliferation and synovial lining formation.

Main Methods:

  • Micromass cultures of FLSs were stimulated with tumor necrosis factor α (TNFα), platelet-derived growth factor (PDGF), and transforming growth factor β (TGFβ).
  • Expression of PI3K isoforms and activation of the PI3K-Akt pathway were analyzed.
  • Small interfering RNA (siRNA) was used to knockdown PI3Kδ in FLSs.

Main Results:

  • Combined stimulation (TPT condition) induced hypertrophic architecture in FLS micromass cultures.
  • TPT condition upregulated matrix metalloproteinase-3 (MMP3), Cadherin-11, and PI3Kδ expression.
  • Knockdown of PI3Kδ significantly inhibited hypertrophic synovial lining formation.

Conclusions:

  • Inducible PI3Kδ is critical for persistent PI3K-Akt activation and hypertrophic synovial lining formation in RA.
  • PI3Kδ represents a potential therapeutic target for managing proliferative synovitis in RA.
Keywords:
Fibroblast-like synoviocytesPDGFPI3K/Akt pathwayPI3KδTGFβ

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

6.0K
Adoptive Immunotherapy of iNKT Cells in Glucose-6-Phosphate Isomerase G6PI-Induced RA Mice08:43

Adoptive Immunotherapy of iNKT Cells in Glucose-6-Phosphate Isomerase G6PI-Induced RA Mice

Published on: January 31, 2020

6.2K

Related Concept Videos

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...
3.2K
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...
10.2K
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...
7.6K
NF-kB-dependent Signaling Pathway02:26

NF-kB-dependent Signaling Pathway

2.0K
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.9K