Pressure and inflammatory stimulation induced increase of cadherin-11 is mediated by PI3K/Akt pathway in synovial fibroblasts from temporomandibular joint.

Abstract

OBJECTIVE:

The goal of the study was to investigate the expression of cadherin-11 in synovial fibroblasts (SFs) under mechanical or inflammatory stimuli, and its potential relationship with PI3K/Akt signaling pathway.

METHODS:

SFs separated from rat temporomandibular joint (TMJ) were treated with hydrostatic pressures (HP) of 30, 60, 90, and 120 kPa, as well as tumor necrosis factor-α (TNF-α) for 12, 24, 48, and 72 h. The location of cadherin-11 was observed by immunofluorescence microscopy, and its expression was detected by real-time PCR and Western blot. We also studied the activation of PI3K/Akt signaling pathway in SFs with HP or TNF-α stimulation.

RESULTS:

The results showed that increased expression of cadherin-11 could be found in the cell-cell contact site of SFs in response to HP and inflammatory stimulation. The mRNA and protein expression of cadherin-11 was positively correlated with the intensity of HP and the duration time of TNF-α treatment. Increased expression of vascular endothelial growth factor-D (VEGF-D) and activation of Akt were also found. Treatment with PI3K inhibitor LY294002 attenuated the pressure or inflammatory cytokine induction increases of cadherin-11, VEGF-D, and FGF-2 both in mRNA and protein levels.

CONCLUSIONS:

These findings suggest that cadherin-11 may play important roles in SFs following exposure to mechanical loading and inflammatory stimulation. In addition, PI3K/Akt pathway was associated with pressure or inflammation-induced cadherin-11 expression, which may involve in the pathogenesis of temporomandibular diseases.

• Authors: M Wu, T Xu, Y Zhou, H Lu, Z Gu
• Journal: Osteoarthritis and cartilage (Osteoarthritis Cartilage) Vol. 21 Issue 10 Pg. 1605-12 (Oct 2013) ISSN: 1522-9653 [Electronic] England
• PMID: 23916685 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Cadherins
• Chromones
• Inflammation Mediators
• Morpholines
• Phosphoinositide-3 Kinase Inhibitors
• RNA, Messenger
• Tumor Necrosis Factor-alpha
• osteoblast cadherin
• 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
• Proto-Oncogene Proteins c-akt

Topics

• Animals
• Cadherins (biosynthesis, genetics)
• Cells, Cultured
• Chromones (pharmacology)
• Fibroblasts (drug effects, metabolism, physiology)
• Gene Expression Regulation (drug effects, physiology)
• Hydrostatic Pressure
• Inflammation Mediators (pharmacology)
• Male
• Mechanotransduction, Cellular (physiology)
• Morpholines (pharmacology)
• Phosphatidylinositol 3-Kinases (physiology)
• Phosphoinositide-3 Kinase Inhibitors
• Proto-Oncogene Proteins c-akt (physiology)
• RNA, Messenger (genetics)
• Rats
• Rats, Sprague-Dawley
• Signal Transduction (physiology)
• Synovial Membrane (cytology, drug effects, metabolism)
• Temporomandibular Joint (cytology, metabolism)
• Tumor Necrosis Factor-alpha (pharmacology)