Role of transient receptor potential vanilloid 4 in rat joint inflammation

Role of transient receptor potential vanilloid 4 in rat joint inflammation

Author Denadai-Souza, Alexandre Autor UNIFESP Google Scholar
Martin, Laurence Google Scholar
Paula, Marco A. Vieira de Google Scholar
Avellar, Maria Christina Werneck Autor UNIFESP Google Scholar
Muscara, Marcelo N. Google Scholar
Vergnolle, Nathalie Google Scholar
Cenac, Nicolas Google Scholar
Institution Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
Univ Toulouse 3
Univ Calgary
Abstract Objective To determine whether activation of transient receptor potential vanilloid 4 (TRPV-4) induces inflammation in the rat temporomandibular joint (TMJ), and to assess the effects of TRPV-4 agonists and proinflammatory mediators, such as a protease-activated receptor 2 (PAR-2) agonist, on TRPV-4 responses. Methods Four hours after intraarticular injection of carrageenan into the rat joints, expression of TRPV-4 and PAR-2 in trigeminal ganglion (TG) neurons and in the TMJs were evaluated by real-time reverse transcriptionpolymerase chain reaction and immunofluorescence, followed by confocal microscopy. the functionality of TRPV-4 and its sensitization by a PAR-2activating peptide (PAR-2AP) were analyzed by measuring the intracellular Ca2+ concentration in TMJ fibroblast-like synovial cells or TG neurons. Plasma extravasation, myeloperoxidase activity, and the head-withdrawal threshold (index of mechanical allodynia) were evaluated after intraarticular injection of selective TRPV-4 agonists, either injected alone or coinjected with PAR-2AP. Results in the rat TMJs, TRPV-4 and PAR-2 expression levels were up-regulated after the induction of inflammation. Two TRPV-4 agonists specifically activated calcium influx in TMJ fibroblast-like synovial cells or TG neurons. in vivo, the agonists triggered dose-dependent increases in plasma extravasation, myeloperoxidase activity, and mechanical allodynia. in synovial cells or TG neurons, pretreatment with PAR-2AP potentiated a TRPV-4 agonistinduced increase in [Ca2+]i. in addition, TRPV-4 agonistinduced inflammation was potentiated by PAR-2AP in vivo. Conclusion in this rat model, TRPV-4 is expressed and functional in TG neurons and synovial cells, and activation of TRPV-4 in vivo causes inflammation in the TMJ. Proinflammatory mediators, such as PAR-2 agonists, sensitize the activity of TRPV-4. These results identify TRPV-4 as an important signal of inflammation in the joint.
Language English
Sponsor INSERM-Avenir
Bettencourt-Schueller Foundation
Foundation for Medical Research
Agence Nationale de la Recherche
Canadian Institute of Health Research
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Grant number FAPESP: 2009/12375-3
Date 2012-06-01
Published in Arthritis and Rheumatism. Hoboken: Wiley-Blackwell, v. 64, n. 6, p. 1848-1858, 2012.
ISSN 0004-3591 (Sherpa/Romeo, impact factor)
Publisher Wiley-Blackwell
Extent 1848-1858
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000304522100018

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