Selective Blockade of Voltage-Gated Potassium Channels Reduces Inflammatory Bone Resorption in Experimental Periodontal Disease

• DOI: 10.1359/jbmr.0301213
• Publication Date: 2006-04-27T05:58:24Z
• Authors: Paloma Valverde; Toshihisa Kawai; Martin A Taubman
• Keywords: 0301 basic medicine; Antigen Presentation; Kv1.3 Potassium Channel; CD3 Complex; Acid Phosphatase; Blotting, Western; Alveolar Bone Loss; Down-Regulation; Gene Expression; Cell Differentiation; Adoptive Transfer; Aggregatibacter actinomycetemcomitans; Coculture Techniques; 3. Good health; Isoenzymes; Interferon-gamma; 03 medical and health sciences; Immunoglobulin G; Animals; Female; Carrier Proteins; Bacterial Outer Membrane Proteins; Glycoproteins

The effects of the potassium channel (Kv1.3) blocker kaliotoxin on T-cell-mediated periodontal bone resorption were examined in rats. Systemic administration abrogated conjunction with decreased RANKL mRNA expression by T-cells gingival tissue. This study suggests a plausible therapeutic approach for inflammatory targeting Kv1.3.Kv1.3 is critical to counterbalance calcium influx at T-cell receptor activation. It not known if Kv1.3 also regulates antigen-activated T-cells, and consequently affects vivo mediated activated T-cells.Actinobacillus actinomycetemcomitans 29-kDa outer membrane protein-specific Th1-clone cells used evaluate (using reverse transcriptase-polymerase chain reaction [RT-PCR] Western blot analyses) (0-100 nM) activation parameters ([3H]thymidine incorporation assays ELISA) osteoprotegerin (OPG; flow cytometry, blot, RT-PCR analyses). A rat disease model based adoptive transfer Th1 clone was analyze alveolar OPG T-cells. Stimulated transferred intravenously day 0 all animals (n = 7 per group). Ten micrograms injected subcutaneously twice days 0, 1, 2, 3, after control group rats saline as placebo same injections kaliotoxin-treated group. MOCP-5 osteoclast precursor cell line co-culture studies fixed measure T-cell-derived RANKL-mediated osteoclastogenesis pit formation vitro. Statistical significance evaluated Student's t-test.Kaliotoxin vitro vivo. Most importantly, resulted an 84% decrease induced saline-treated recovered from tissue displayed lower ratios than those ratio protein induction RANKL-dependent markedly treatments vitro.The use or other means block may constitute potential intervention therapy prevent loss disease.