Potassium channel-blockers as therapeutic agents to interfere with bone resorption of periodontal disease

Journal of Dental Research

Volumn 84, Issue 6, 2005, Pages 488-499

  Valverde, P ^a   Kawai, T ^b   Taubman, M A ^b  

^a TUFTS UNIVERSITY SCHOOL OF DENTAL MEDICINE   (United States)

^b FORSYTH INSTITUTE   (United States)

Author keywords

IKCa1; Kv1.3; Periodontal disease; Potassium channel blockers; RANKL

Indexed keywords

CARRIER PROTEIN; INTERMEDIATE CONDUCTANCE CALCIUM ACTIVATED POTASSIUM CHANNEL; KCNA3 PROTEIN, HUMAN; KCNN4 PROTEIN, HUMAN; LIGAND; MEMBRANE PROTEIN; OSTEOCLAST DIFFERENTIATION FACTOR; POTASSIUM CHANNEL; POTASSIUM CHANNEL BLOCKING AGENT; POTASSIUM CHANNEL KV1.3; RECEPTOR ACTIVATOR OF NUCLEAR FACTOR KAPPA B; TNFRSF11A PROTEIN, HUMAN; TNFSF11 PROTEIN, HUMAN; TUMOR NECROSIS FACTOR ALPHA; TUMOR NECROSIS FACTOR RECEPTOR; VOLTAGE GATED POTASSIUM CHANNEL;

DRUG ANTAGONISM; DRUG EFFECT; HUMAN; IMMUNOLOGY; OSTEOLYSIS; PERIODONTAL DISEASE; REVIEW;

ALVEOLAR BONE LOSS; BONE RESORPTION; CARRIER PROTEINS; HUMANS; INTERMEDIATE-CONDUCTANCE CALCIUM-ACTIVATED POTASSIUM CHANNELS; KV1.3 POTASSIUM CHANNEL; LIGANDS; MEMBRANE GLYCOPROTEINS; PERIODONTAL DISEASES; POTASSIUM CHANNEL BLOCKERS; POTASSIUM CHANNELS; POTASSIUM CHANNELS, VOLTAGE-GATED; RANK LIGAND; RECEPTOR ACTIVATOR OF NUCLEAR FACTOR-KAPPA B; RECEPTORS, TUMOR NECROSIS FACTOR; TUMOR NECROSIS FACTOR-ALPHA;

EID: 22844443254     PISSN: 00220345     EISSN: None     Source Type: Journal    
DOI: 10.1177/154405910508400603     Document Type: Review

References (128)

1. Akatsu T, Murakami T, Nishakawa N, Ono K, Shinomiya N, Tsuda E, et al. (1998). Osteoclastogenesis-inhibitory factor suppresses osteoclast survival by interfering in the interaction of stromal cells with osteoclasts. Biochem Biophys Res Commun 250:229-234.
2. + channels. J Immunol 144:2038-2045.
3. Arkett SA, Dixon SJ, Sims SM (1992). Substrate influences rat osteoclast morphology and expression of potassium conductances. J Physiol 458:633-653.
4. Arkett SA, Dixon J, Yang JN, Sakai DD, Minkin C, Sims SM (1994). Mammalian osteoclasts express a transient potassium channel with properties of Kv1.3. Receptors Channels 2:281-293.
5. Atkinson MA, Eisenbarth GS (2001). Type 1 diabetes: new perspectives on disease pathogenesis and treatment. Lancet 358:221-229.
6. Baier G (2003). The PKC gene module: molecular biosystematics to resolve its T cell functions. Immunol Rev 192:64-79.
7. Baker PJ (2000). The role of immune responses in bone loss during periodontal disease. Microbes Infect 2:1181-1192.
8. Baker PJ, Carter S, Dixon M, Evans RT, Roopenian DC (1999a). Serum antibody response to oral infection precedes but does not prevent Porphyromonas gingivalis-induced alveolar bone loss in mice. Oral Microbiol Immunol 14:194-196.
9. +) T cells and the proinflammatory cytokines gamma interferon and interleukin-6 contribute to alveolar bone loss in mice. Infect Immun 67:2804-2809.
10. Bang J, Cimasoni G, Rosenbusch C, Duckert A (1973). Sodium, potassium and calcium contents of crevicular exudates: their relations to gingivitis and periodontitis. J Periodontol 44:770-774.
11. + channels improves experimental autoimmune encephalomyelitis and inhibits T cell activation. J Immunol 166:936-944.
12. + channels ameliorates experimental autoimmune encephalomyelitis, a model for multiple sclerosis. Proc Natl Acad Sci USA 98:13942-13947.
13. Bekker PJ, Holloway D, Nakanishi A, Arrighi M, Leese PT, Dunstan CR (2001). The effect of a single dose of osteoprotegerin in postmenopausal women. J Bone Miner Res 1:348-360.
14. Bharti AC, Takada Y, Shishodia S, Aggarwal BB (2004). Evidence that receptor activator of nuclear factor (NF)-kappaB ligand can suppress cell proliferation and induce apoptosis through activation of a NF-kappaB-independent and TRAF6-dependent mechanism. J Biol Chem 279:6065-6076.
15. Bishop GA, Hostager BS (2003). The CD40-CD154 interaction in B cell-T cell liaisons. Cytokine Growth Factor Rev 14:297-309.
16. Boltchi FE, Rees TD, Iacopino AM (1999). Cyclosporine A-induced gingival overgrowth: a comprehensive review. Quintessence Int 30:775-783.
17. Brent LH, Butler JL, Woods WT, Bubien JK (1990). Transmembrane ion conductance in human B lymphocyte activation. J Immunol 145:2381-2389.
18. Cahalan MD, Wulff H, Chandy KG (2001). Molecular properties and physiological roles of ion channels in the immune system. J Clin Immunol 11:235-252.
19. 2+-activated potassium channels. Mol Pharmacol 63:409-418.
20. Cayco AV, Wysolmerski J, Simpson C, Mitnick MA, Gundberg C, Kliger A, et al. (2000). Posttransplant bone disease: evidence for a high bone resorption state. Transplantation 70:1722-1728.
21. Chandy KG, Cahalan M, Pennington M, Norton RS, Wulff H, Gutman GA (2001). Potassium channels in T lymphocytes: toxins to therapeutic immunosuppressants. Toxicon 39:1269-1276.
22. + channels as targets for specific immunomodulation. Trends Pharmacolog Sci 25:280-289.
23. Choi Y, Kim JJ (2003). B cells activated in the presence of Th1 cytokines inhibit osteoclastogenesis. Exp Mol Med 35:385-392.
24. + T cells. Eur J Immunol 31:2179-2188.
25. Choo MJ, Chole RA (1999). Cytochrome P-450 inhibition blocks bone resorption in vitro and in vivo. Otolaryngol Head Neck Surg 120:84-91.
26. Clark WB, Löe H (1993). Mechanisms of initiation and progression of periodontal disease. Periodontol 2000 2:72-82.
27. 2+, calcineurin, and NFAT. Cell 96:611-614.
28. Curtis MA, Aduse-Opoku J, Rangarajan M (2001). Cysteine proteases of Porphyromonas gingivalis. Crit Rev Oral Biol Med 12:192-216.
29. Cutler CW, Jotwani R (2004). Antigen-presentation and the role of dendritic cells in periodontitis. Periodontol 2000 35:135-157.
30. Dorner T, Burmester GR (2003). The role of B cells in rheumatoid arthritis: mechanisms and therapeutic targets. Curr Opin Rheumatol 15:246-252.
31. Ducy P, Schinke T, Karsenty G (2000). The osteoblast: a sophisticated fibroblast under central surveillance. Science 289:1501-1504.
32. Dzink JL, Tanner ACR, Haffajee AD, Socransky SS (1985). Gram negative species associated with active destructive periodontal lesions. J Clin Periodontol 12:648-659.
33. Ebersole JL, Taubman MA (1994). The protective nature of host responses in periodontal diseases. Periodontol 2000 5:112-141.
34. Epstein S (1996). Post-transplantation bone disease: the role of immunosuppressive agents and the skeleton. J Bone Miner Res 11:1-7.
35. Espinosa L, Paret L, Ojeda C, Tourneur Y, Delmas PD, Chenu C (2002). Osteoclast spreading kinetics are correlated with an oscillatory activation of a calcium-dependent potassium current. J Cell Sci 115:3837-3848.
36. Fanger CM, Rauer H, Neben AL, Miller MJ, Rauer H, Wulff H, et al. (2001). Calcium-activated potassium channels sustain calcium signaling in T lymphocytes. Selective blockers and manipulated channel expression levels. J Biol Chem 276:12249-12256.
37. Flanagan AM, Massay HM (2003). Generating human osteoclasts in vitro from bone marrow and peripheral blood. Methods Mol Med 80:113-128.
38. + T cells isolated from human gingival tissues. Clin Exp Immunol 103:422-428.
39. Gemmell E, Seymour GJ (1991). Phenotypic analysis of B-cells extracted from human periodontal disease tissue. Oral Microbiol Immunol 6:356-362.
40. Gemmell E, Feldner B, Seymour GJ (1992). CD45RA and CD45RO positive CD4 cells in human peripheral blood and periodontal disease tissue before and after stimulation with periodontopathic bacteria. Oral Microbiol Immunol 7:84-88.
41. Grewal IS, Flavell RA (1998). CD40 and CD154 in cell-mediated immunity. Annu Rev Immunol 16:111-135.
42. Griffen AL, Lyons SR, Becker MR, Moeschberger ME, Leys EJ (1999). Porphyromonas gingivalis strain variability and periodontitis. J Clin Microbiol 37:4028-4033.
43. + channels, types Kv1.1, 1.2, 1.3, 1.5, and 3.1, stably expressed in mammalian cell lines. Mol Pharmacol 45:1227-1234.
44. Gulbis JM, Doyle D (2004). Potassium channel structures: do they conform? Curr Opin Struct Biol 14:440-446.
45. Hanner M, Schmalhofer WA, Green B, Bordallo C, Liu J, Slaugher RS, et al. (1999). Binding of correolide to K(v)1 family potassium channels. Mapping the domains of high affinity interaction. J Biol Chem 274:25237-25244.
46. Hayashi S, Yamada T, Tsuneto M, Yamane T, Takahashi M, Shultz LD, et al. (2003). Distinct osteoclast precursors in the bone marrow and extramedullary organs characterized by responsiveness to Toll-like receptor ligands and TNF-alpha. J Immunol 171:5130-5139.
47. Henderson B, Nair SP, Ward JM, Wilson M (2003). Molecular pathogenicity of the oral opportunistic pathogen Actinobacillus actinomycetemcomitans. Annu Rev Microbiol 57:29-55.
48. Hille B (2001). Ionic channels of excitable membranes. 3rd ed. Sunderland, MA: Sinauer Associates.
49. Hirotani H, Tuohy NA, Woo JT, Stern PH, Clipstone NA (2004). The calcineurin/nuclear factor of activated T cells signaling pathway regulates osteoclastogenesis in RAW264.7 cells. J Biol Chem 279:13984-13992.
50. Hofbauer LC, Heufelder AE (2001). Role of receptor activator of nuclear factor-kB ligand and osteoprotegerin in bone cell biology. J Mol Med 79:243-253.
51. Hofbauer LC, Shue C, Riggs BL, Dunstan CR, Spelsberg TC, O'Brian T, et al. (2001). Effects of immunosuppressants on receptor activator of NF-κB ligand and osteoprotegerin production by human osteoblastic and coronary artery smooth muscle cells. Biochem Biophys Res Commun 280:334-339.
52. Horowitz MC, Lorenzo JA (2004). The origins of osteoclasts. Curr Opin Rheumatol 16:464-468.
53. Hou L, Sasaki H, Stashenko P (2000). B-cell deficiency predisposes mice to disseminating anaerobic infections: protection by passive antibody transfer. Infect Immun 68:5645-5651.
54. Igarashi K, Hirotani H, Woo JT, Stern PH (2004). Cyclosporin A and FK506 induce osteoclast apoptosis in mouse bone marrow cell cultures. Bone 35:47-56.
55. Iglesias A, Bauer J, Litzenburger T, Schubart A, Linington C (2001). T- and B-cell responses to myelin oligodendrocyte glycoprotein in experimental autoimmune encephalomyelitis and multiple sclerosis. Glia 36:220-234.
56. + channel of intermediate conductance: a molecular target for novel treatments? Curr Drug Targets 2:401-422.
57. + channel. Nature 423:33-41.
58. 2+ concentration in rat osteoclasts. Am J Physiol Cell Physiol 285:C457-C466.
59. Kawai T, Eisen-Lev R, Seki M, Eastcott JW, Wilson ME, Taubman MA (2000). Requirement of B7 costimulation for Th1-mediated inflammatory bone resorption in experimental periodontal disease. J Immunol 164:2102-2109.
60. Khapli SM, Mangashetti LS, Yogesha SD, Wani MR (2003). IL-3 acts directly on osteoclast precursors and irreversibly inhibits receptor activator of NF-kappa B ligand-induced osteoclast differentiation by diverting the cells to macrophage lineage. J Immunol 171:142-151.
61. Khoori AH, Einollahi B, Ansari G, Moozeh MB (2003). The effect of cyclosporine with or without nifedipine on gingival overgrowth in renal transplant patients. J Can Dent Assoc 69:236-241.
62. Khosla S (2001). Minireview: the OPG/RANKL/RANK system. Endocrinology 142:5050-5055.
63. Kinane DF, Jonston FA, Evans CW (1989). Depressed helper-to-suppressor T-cell ratios in early-onset forms of periodontal disease. J Periodontal Res 24:161-164.
64. Komarova SV, Dixon SJ, Sims SM (2001). Osteoclast ion channels: potential targets for antiresorptive drugs. Curr Pharmaceut Design 7:637-654.
65. 2+ accelerates nuclear translocation of nuclear factor kB in osteoclasts. J Biol Chem 278:8286-8293.
66. Kong YY, Yoshida H, Sarosi I, Tan HL, Timms E, Capparelli C, et al. (1999a). OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature 397:315-323.
67. Kong YY, Feige U, Sarosi I, Bolon B, Tafuri A, Moroni S, et al. (1999b). Activated T cells regulate bone loss and joint destruction in arthritis via OGPL. Nature 402:304-309.
68. Koo GC, Blake JT, Talento A, Nguyen M, Lin S, Sirotina A, et al. (1997). Blockade of the voltage-gated potassium channel Kv1.3 inhibits immune responses in vivo. J Immunol 158:5120-5128.
69. Koo GC, Blake JT, Shah K, Staruch MJ, Dumont F, Wunderler D, et al. (1999). Correolide and derivatives are novel immunosuppressants blocking the lymphocyte Kv1.3 potassium channels. Cell Immunol 197:99-107.
70. Krogsgaard M, Huppa JB, Purbhoo MA, Davis MM (2003). Linking molecular and cellular events in T-cell activation and synapse formation. Semin Immunol 15:307-315.
71. Kwan Tat S, Padrines M, Theoleyre S, Heymann D, Fortun Y (2004). IL-6, RANKL, TNF-alpha/IL-1: interrelations in bone resoption pathophysiology. Cytokine Growth Factor Rev 15:49-60.
72. Lacey DL, Timms E, Tan HL, Kelley MJ, Dunstan CR, Burgess T, et al. (1998). Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 93:165-176.
73. Lee ZH, Kim HH (2003). Signal transduction by receptor activator of nuclear factor kappa B in osteoclasts. Biochem Biophys Res Commun 305:211-214.
74. +) and opening of voltage-gated potassium channels activate T cell integrin function: physical and functional association between Kv1.3 channels and beta1 integrins. J Exp Med 191:1167-1176.
75. Manabe N, Kawaguchi H, Chikuda H, Miyaura C, Inada M, Nagai R, et al. (2001). Connection between B lymphocyte and osteoclast differentiation pathways. J Immunol 167:2625-2631.
76. Mogi M, Otogoto J, Ota N, Togari A (2004). Differential expression of RANKL and osteoprotegerin in gingival crevicular fluid of patients with periodontitis. J Dent Res 83:166-169.
77. O'Connor KC, Bar-Or A, Hafler DA (2001). The neuroimmunology of multiple sclerosis: possible roles of T and B lymphocytes in immunopathogenesis. J Clin Immunol 21:81-92.
78. O'Sullivan B, Thomas R (2003). CD40 and dendritic cell function. Crit Rev Immunol 23:83-107.
79. Ohta H, Inoue T, Fukui K (2001). Energy metabolism of Actinobacillus actinomycetemcomitans during anaerobic and microaerobic growth in low- and high-potassium continuous culture. Microbiology 147:2461-2468.
80. Page RC, Schroeder HA (1976). Pathogenesis of inflammatory periodontal disease. A summary of current work. Lab Invest 34:235-249.
81. Panayi GS (1995). Treating rheumatoid arthritis with clotrimazole. Nat Med 1:977-978.
82. Partiseti M, Choquet D, Diu A, Korn H (1992). Differential regulation of voltage- and calcium-activated potassium channels in human B lymphocytes. J Immunol 148:3361-3368.
83. Partiseti M, Korn H, Choquet D (1993). Pattern of potassium channel expression in proliferating B lymphocytes depends upon the mode of activation. J Immunol 151:2462-2470.
84. 2+ signalling". Biol Cell 96:69-78.
85. Rifkin BR, Vernillo AT, Golub LM (1993). Blocking periodontal disease progression by inhibiting tissue-destructive enzymes: a potential therapeutic role for tetracyclines and their chemically-modified analogs. J Periodontol 64:819-827.
86. Roberts AI, Devadas S, Zhang X, Zhang L, Keegan A, Greeneltch K, et al. (2003). The role of activation-induced cell death in the differentiation of T-helper-cell subsets. Immunol Res 28:285-293.
87. Sallusto F, Geginat J, Lanzavecchia A (2004). Central memory and effector memory T cell subsets: function, generation and maintenance. Annu Rev Immunol 22:745-763.
88. Schmalhofer WA, Bao J, McManus OB, Green B, Matyskiela M, Wunderler D, et al. (2002). Identification of a new class of inhibitors of the voltage-gated potassium channel, Kv1.3, with immunosuppressant properties. Biochemistry 41:7781-7794.
89. Schett G, Redlich K, Hayer S, Zwerina J, Bolon B, Dunstan C, et al. (2003). Osteoprotegerin protects against generalized bone loss in tumor necrosis factor-transgenic mice. Arthritis Rheum 48:2042-2051.
90. Seymour GJ (1991). Importance of the host response in the periodontium. J Clin Periodontol 18:421-426.
91. Socransky SS, Haffajee AD, Cugini MA, Smith C, Kent RLJ (1998). Microbial complexes in subgingival plaque. J Clin Periodontol 25:134-144.
92. Socransky SS, Haffajee AD, Ximenez-Fyvie LA, Feres M, Mager D (2000). Ecological considerations in the treatment of Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis periodontal infections. Periodontol 2000 20:341-362.
93. Stocker JW, De Franceschi L, McNaughton-Smith GA, Corrocher R, Beuzard Y, Brugnara C (2003). ICA-17043, a novel Gardos channel blocker, prevents sickled red blood cell dehydration in vitro and in vivo in SAD mice. Blood 101:2412-2418.
94. Sugai M, Kawamoto T, Peres SY, Ueno Y, Komatsuzawa H, Fujiwara T, et al. (1998). The cell cycle-specific growth-inhibitory factor produced by Actinobacillus actinomycetemcomitans is a cytolethal distending toxin. Infect Immun 66:5008-5019.
95. Susa M, Luong-Nguyen N-H, Cappellen D, Zamurovic N, Gamse R (2004). Human primary osteoclasts: in vitro generation and applications as pharmacological and clinical assay. J Translational Med 2:6-10.
96. Sutro JB, Vayuvegula BS, Gupta S, Cahalan MD (1989). Voltage-sensitive ion channels in human B lymphocytes. Adv Exp Med Biol 254:113-122.
97. Takayanagi H, Kim S, Koga T, Nishina H, Isshiki M, Yoshida H, et al. (2002). Induction and activation of the transcription factor NFATc1 (NFAT2) integrate RANKL signaling in terminal differentiation of osteoclasts. Dev Cell 3:889-901.
98. Takeichi O, Haber J, Kawai T, Smith DJ, Moro I, Taubman MA (2000). Cytokine profiles of T-lymphocytes from gingival tissues with pathological pocketing. J Dent Res 79:1548-1555.
99. Tatevossian A, Gould CT (1976). The composition of the aqueous phase in human dental plaque. Arch Oral Biol 21:319-323.
100. Taubman MA, Kawai T (2001). Involvement of T-lymphocytes in periodontal disease and in direct and indirect induction of bone resoption. Crit Rev Oral Biol Med 12:125-135.
101. Taubman MA, Ebersole JL, Smith DJ (1982). Association between systemic and local antibody and periodontal diseases. In: Host parasite interactions in periodontal diseases. Genco R, Mergenhagen SE, editors. Washington, DC: ASM Press, pp. 283-298.
102. Taubman MA, Eastcott JW, Shimauchi H, Takeichi O, Smith DJ (1994). Modulatory role of T lymphocytes in periodontal inflammation. In: Molecular pathogenesis of periodontal disease. Genco R, Hamada S, Lehner T, McGhee JR, Mergenhagen SE, editors. Washington, DC: ASM Press, pp. 147-157.
103. Teitelbaum SL (2000). Bone resorption by osteoclasts. Science 289:1504-1508.
104. Teng Y-TA (2003). The role of acquired immunity and periodontal disease progression. Crit Rev Oral Biol Med 14:237-252.
105. Teng Y-TA, Nguyen H, Hassanloo A, Ellen RP, Hozumi H, Gorczynski RM (1999). Periodontal immune responses of human lymphocytes in Actinobacillus actinomycetemcomitans-inoculatea NOD/SCID mice engrafted with peripheral blood leukocytes of periodontitis patients. J Periodontal Res 34:54-61.
106. Teng Y-TA, Nguyen H, Gao X, Kong Y, Gorczynski RM, Singh B, et al. (2000). Functional human T-cell immunity and osteoprotegerin ligand control alveolar bone destruction in periodontal infection. J Clin Invest 106:59-67.
107. Theill LE, Boyle WJ, Penninger JM (2002). RANKL and RANK: T cells, bone loss and mammalian evolution. Annu Rev Immunol 20:795-823.
108. Toraldo G, Roggia C, Qian WP, Pacifici R, Weitzmann MN (2003). IL-7 induces bone loss in vivo by induction of receptor activator of nuclear factor kappa B ligand and tumor necrosis factor alpha from T cells. Proc Natl Acad Sci USA 100:125-130.
109. Tsai CC, McArthur WP, Baehni PC, Hammond BF, Taichman NS (1979). Extraction and partial characterization of a leukotoxin from a plaque-derived Gram-negative microorganism. Infect Immun 25:427-439.
110. Valverde P, Kawai T, Taubman MA (2004). Selective blockade of voltage-gated potassium channels reduces inflammatory bone resorption in experimental periodontal disease. J Bone Miner Res 19:155-164.
111. Vennekamp J, Wulff H, Beeton C, Calabresi PA, Grissmer S, Hansel W, et al. (2004). Kv1.3 blocking 5-phenylalkoxypsoralens: a new class of immunomodulators. Mol Pharmacol 65:1364-1374.
112. + channel responses during proliferation and activation in macrophages. J Biol Chem 278:46307-46320.
113. + channel expression in brain via TNF-alpha-dependent and -independent pathways. FEBS Lett 572:189-194.
114. Viglietta V, Kent SC, Orban T, Hafler DA (2002). GAD65-reactive T cells are activated in patients with autoimmune type 1a diabetes. J Clin Invest 109:895-903.
115. Wang R, Zhang L, Shang X, Moreno J, Celluzzi C, Tondravi M, et al. (2002). Regulation of activation-induced receptor activator of NF-kB ligand (RANKL) expression in T cells. Eur J Immunol 32:1090-1098.
116. Wilson ME (1991). IgG antibody response of localized juvenile periodontitis patients to the 29 kilodalton outer membrane protein of Actinobacillus actinomycetemcomitans. J Periodontol 62:211-218.
117. Wilson M (1995). Biological activities of lipopolysaccharides from oral bacteria and their relevance to the pathogenesis of chronic periodontitis. Sci Pro 78:19-34.
118. Wittrant Y, Theoleyre S, Chipoy C, Padrines M, Blanchard F, Heymann D, et al. (2004). RANKL/RANK/OPG: new therapeutic targets in bone tumours and associated osteolysis. Biochim Biophys Acta 1704:49-57.
119. Wu X, Pan G, McKenna MA, Zayzafoon M, Xiong W-C, McDonald J (2005). RANKL regulates Fas expression and Fas-mediated apoptosis in osteoclasts. J Bone Miner Res 20:107-116.
120. + channel, IKCa1: a potential immunosuppressant. Proc Natl Acad Sci USA 97:8151-8156.
121. Wulff H, Beeton C, Chandy KG (2003a). Potassium channels as therapeutic targets for autoimmune disorders. Curr Opin Drug Discov Devel 6:640-647.
122. +) channel in effector memory T cells as new target for MS. J Clin Invest 111:1703-1713.
123. + channel expression during B-cell differentiation: implications for immunomodulation and autoimmunity. J Immunol 173:776-786.
124. Yamazaki K, Nakajima T, Aoyagi T, Hara K (1993). Immunohistological analysis of memory T lymphocytes and activated B lymphocytes in tissue with periodontal disease. J Periodontal Res 28:324-334.
125. Yasuda H, Shima N, Nakagawa N, Yamaguchi K, Kinosaki M, Mochizuki S, et al. (1998). Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci USA 95:3597-3602.
126. Yu FH, Catterall WA (2004). The VGL-chanome: a protein superfamily specialized for electrical signaling and ionic homeostasis. Sci STKE 253:15-20.
127. Yun TJ, Chaudhary PM, Shu GL, Frazer JK, Ewings MK, Schwartz SM, et al. (1998). OPG/FDCR-1, a TNF receptor family member, is expressed in lymphoid cells and is up-regulated by ligating CD40. J Immunol 161:6113-6121.
128. Zauli G, Rimondi E, Nicolin V, Melloni E, Celeghini C, Secchiero P (2004). TNF-related apoptosis-inducing ligand (TRAIL) blocks osteoclastic differentiation induced by RANKL plus M-CSF. Blood 104:2044-2050.