title: 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.affiliation: Department of Orthodontics, Hospital of Stomatology, Zhejiang University, 395 Yan'an Road, Hangzhou 310006, China.
authors.forename: M
authors.initials: M
authors.lastname: Wu
authors.forename: T
authors.initials: T
authors.lastname: Xu
authors.forename: Y
authors.initials: Y
authors.lastname: Zhou
authors.forename: H
authors.initials: H
authors.lastname: Lu
authors.forename: Z
authors.initials: Z
authors.lastname: Gu
mesh_terms: D000818:Animals; D015820:Cadherins / Q000096:biosynthesis* / Q000235:genetics; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006874:Hydrostatic Pressure; D018836:Inflammation Mediators / Q000494:pharmacology; D008297:Male; D040542:Mechanotransduction, Cellular / Q000502:physiology; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D013583:Synovial Membrane / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D013704:Temporomandibular Joint / Q000166:cytology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D015820:Cadherins; D002867:Chromones; D018836:Inflammation Mediators; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C086960:osteoblast cadherin; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
keywords: Cadherin-11; Hydrostatic pressure; Synovial fibroblasts; TNF-α; Temporomandibular disorders