Knockdown of Fcγ receptor III in an arthritic temporomandibular joint reduces the nociceptive response in rats.
OBJECTIVE
Fcγ receptor III (FcγRIII; 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 FcγRIII 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. FcγRIII expression in the TMJ tissue was assayed by immunocytochemistry or Western blotting. Cleavage of FcγRIII transcript was then assayed by 5' rapid amplification of complementary DNA ends. Interleukin-1β (IL-1β) and IgG content was measured in the TMJ tissue by enzyme-linked immunosorbent assay.


RESULTS
Injection of FcγRIII siRNA reduced the amount of FcγRIII in the TMJ tissues, and the transcript was cleaved in a manner consistent with an RNA interference mechanism. Moreover, injection of FcγRIII siRNA reduced the nociceptive response of rats with an arthritic TMJ and reduced the amount of the proinflammatory cytokine IL-1β.


CONCLUSIONS
FcγRIII contributes to the pain resulting from inflammatory arthritis of the TMJ, and siRNA has the potential to be an effective treatment for this disorder.
Kramer
Phillip R
PR
Texas A&M Health Science Center and Baylor College of Dentistry, Dallas. TX. USA. pkramer@bcd.tamhsc.edu
Puri
Jyoti
J
Bellinger
Larry L
LL
D000818:Animals; D018771:Arthralgia / Q000503:physiopathology* / Q000517:prevention & control; D001169:Arthritis, Experimental; D001172:Arthritis, Rheumatoid / Q000503:physiopathology*; D001685:Biological Factors / Q000494:pharmacology; D004195:Disease Models, Animal; D008297:Male; D009619:Nociceptors; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017452:Receptors, IgG / Q000502:physiology*; D013704:Temporomandibular Joint / Q000503:physiopathology*
D001685:Biological Factors; D034741:RNA, Small Interfering; D017452:Receptors, IgG