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Title: Role of transient receptor potential vanilloid 4 in rat joint inflammation
Authors: Denadai-Souza, Alexandre [UNIFESP]
Martin, Laurence
Paula, Marco A. Vieira de
Avellar, Maria Christina Werneck [UNIFESP]
Muscara, Marcelo N.
Vergnolle, Nathalie
Cenac, Nicolas
Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
Univ Toulouse 3
Univ Calgary
Issue Date: 1-Jun-2012
Publisher: Wiley-Blackwell
Citation: Arthritis and Rheumatism. Hoboken: Wiley-Blackwell, v. 64, n. 6, p. 1848-1858, 2012.
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.
ISSN: 0004-3591
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