Role of transient receptor potential vanilloid 4 in rat joint inflammation

Author(s)

Denadai-Souza, Alexandre ^{[1, 2, 3, 4]} ; Martin, Laurence ^{[3, 4]} ; de Paula, Marco A. Vieira ^[2] ; de Avellar, Maria C. Werneck ^[1] ; Muscara, Marcelo N. ^[2] ; Vergnolle, Nathalie ^{[3, 4, 5]} ; Cenac, Nicolas ^{[3, 4]}

Affiliation

^[1] Univ Fed Sao Paulo, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Sao Paulo - Brazil

^[3] Univ Toulouse 3, Ctr Physiopathol Toulouse Purpan, INSERM, U1043, F-31062 Toulouse - France

^[4] CNRS, U5282, Toulouse - France

^[5] Univ Calgary, Calgary, AB - Canada

• Document type: Journal article
• Source: ARTHRITIS AND RHEUMATISM; v. 64, n. 6, p. 1848-1858, JUN 2012.
• Web of Science Citations: 26

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. (AU)

• FAPESP's process: 09/12375-3 - Role of the protein SPAG11 in the modulation of experimental arthritis
• Grantee: Alexandre Denadai Souza
• Support Opportunities: Scholarships in Brazil - Post-Doctoral