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Knockdown of Fcgamma receptor III in an arthritic temporomandibular joint reduces the nociceptive response in rats.

Authors: Kramer, PR  Puri, J  Bellinger, LL 
Citation: Kramer PR, etal., Arthritis Rheum. 2010 Oct;62(10):3109-18.
Pubmed: (View Article at PubMed) PMID:20589683
DOI: Full-text: DOI:10.1002/art.27630

OBJECTIVE: Fcgamma receptor III (FcgammaRIII; CD16) is a receptor expressed on immune cells that selectively binds IgG molecules. IgG binding results in cellular activation and cytokine release. IgG is an important factor in arthritis and can be found in the arthritic temporomandibular joint (TMJ). We undertook this study to test the hypothesis that a reduction in FcgammaRIII expression in TMJ tissues would reduce the nociceptive and inflammatory responses in an inflamed joint. METHODS: Small interfering RNA (siRNA), either naked or complexed with linear polyethyleneimine, was injected into the superior joint space of the TMJ in rats. After administration of siRNA the joint was injected with saline or with Freund's complete adjuvant to induce arthritis. Nociceptive responses were quantitated in the rat by measuring the animal's meal duration. FcgammaRIII expression in the TMJ tissue was assayed by immunocytochemistry or Western blotting. Cleavage of FcgammaRIII transcript was then assayed by 5' rapid amplification of complementary DNA ends. Interleukin-1beta (IL-1beta) and IgG content was measured in the TMJ tissue by enzyme-linked immunosorbent assay. RESULTS: Injection of FcgammaRIII siRNA reduced the amount of FcgammaRIII in the TMJ tissues, and the transcript was cleaved in a manner consistent with an RNA interference mechanism. Moreover, injection of FcgammaRIII siRNA reduced the nociceptive response of rats with an arthritic TMJ and reduced the amount of the proinflammatory cytokine IL-1beta. CONCLUSION: FcgammaRIII contributes to the pain resulting from inflammatory arthritis of the TMJ, and siRNA has the potential to be an effective treatment for this disorder.


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CRRD Object Information
CRRD ID: 5508377
Created: 2011-10-13
Species: All species
Last Modified: 2011-10-13
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.