Cell-based assay strategy for identification of motif-specific RANK signaling pathway inhibitors

Assay and Drug Development Technologies

Volumn 4, Issue 4, 2006, Pages 473-482

  Chen, Taosheng ^a   Xu, Feng ^b  

^a BRISTOL MYERS SQUIBB   (United States)

^b University of Alabama at Birmingham   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIRESORPTIVE AGENT; CYTOKINE ANTIBODY; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; LUCIFERASE; NEW DRUG; OSTEOCLAST DIFFERENTIATION FACTOR; OSTEOCLAST DIFFERENTIATION FACTOR ANTIBODY; OSTEOPROTEGERIN; TUMOR NECROSIS FACTOR RECEPTOR ASSOCIATED FACTOR; UNCLASSIFIED DRUG;

BINDING SITE; BONE DISEASE; BONE MARROW; CELL ASSAY; CELL MATURATION; DRUG SCREENING; DRUG TARGETING; GENE EXPRESSION REGULATION; HIGH THROUGHPUT SCREENING; HUMAN; MACROPHAGE; NONHUMAN; OSTEOCLAST; PROTEIN BINDING; PROTEIN FUNCTION; PROTEIN MOTIF; PROTEIN PROTEIN INTERACTION; REVIEW; SIGNAL TRANSDUCTION;

AMINO ACID SEQUENCE; BONE RESORPTION; DRUG DESIGN; HUMANS; MOLECULAR SEQUENCE DATA; OSTEOCLASTS; OSTEOPROTEGERIN; RANK LIGAND; RECEPTOR ACTIVATOR OF NUCLEAR FACTOR-KAPPA B; SIGNAL TRANSDUCTION;

EID: 33751285801     PISSN: 1540658X     EISSN: None     Source Type: Journal    
DOI: 10.1089/adt.2006.4.473     Document Type: Review

References (61)

1. Ross FP, Teitelbaum SL: Osteoclast biology. In: Osteoporosis, 2nd ed. (Marcus R, Feldman D, Kelsey J, eds.), pp. 73-106. Academic Press, San Diego, 2001.
2. Teitelbaum SL: Bone resorption by osteoclasts. Science 2000;289:1504-1508.
3. Teitelbaum SL, Ross FP: Genetic regulation of osteoclast development and function. Nat Rev Genet 2003;4:638-649.
4. Boyle WJ, Simonet WS, Lacey DL: Osteoclast differentiation and activation. Nature 2003;423:337-342.
5. Lee CA, Einhorn TA: The bone organ system: form and function. In: Osteoporosis, 2nd ed. (Marcus R, Feldman D, Kelsey J, eds.), pp. 3-21. Academic Press, San Diego, 2001.
6. Baron R: General principle of bone biology. In: Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, 5th ed. (Favus MJ, ed.), pp. 1-8. American Society for Bone and Mineral Research, Washington, DC, 2003.
7. Martin TJ, Rodan GA: Coupling of bone resorption and formation during bone remodeling. In: Osteoporosis, 2nd ed. (Marcus R, Feldman D, Kelsey J, eds.), pp. 361-372. Academic Press, San Diego, 2001.
8. Goldring SR: Pathogenesis of bone and cartilage destruction in rheumatoid arthritis. Rheumatology 2003;42(Suppl 2):ii11-ii16.
9. Mundy GR: Metastasis to bone: causes, consequences and therapeutic opportunities. Nat Rev 2002;2:584-593.
10. Stepan JJ, Alenfeld F, Boivin G, Feyen JH, Lakatos P: Mechanisms of action of antiresorptive therapies of postmenopausal osteoporosis. Endocr Regul 2003;37:225-238.
11. Lufkin EG, Sarkar S, Kulkarni PM, Ciaccia AV, Siddhanti S, Stock J, Plouffe L Jr: Antiresorptive treatment of postmenopausal osteoporosis: review of randomized clinical studies and rationale for the Evista alendronate comparison (EVA) trial. Curr Med Res Opin 2004;20:351-357.
12. Marcus R, Wong M, Heath H III, Stock JL: Antiresorptive treatment of postmenopausal osteoporosis: comparison of study designs and outcomes in large clinical trials with fracture as an endpoint. Endocr Rev 2002;23:16-37.
13. Lacey DL, Timms E, Tan HL, Kelley MJ, Dunstan CR, Burgess T, Elliott R, Colombero A, Elliott G, Scully S, Hsu H, Sullivan J, Hawkins N, Davy E, Capparelli C, Eli A, Qian YX, Kaufman S, Sarosi I, Shalhoub V, Senaldi G, Guo J, Delaney J, Boyle WJ: Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 1998;93:165-176.
14. Yasuda H, Shima N, Nakagawa N, Yamaguchi K, Kinosaki M, Mochizuki S, Tomoyasu A, Yano K, Goto M, Murakami A, Tsuda E, Morinaga T, Higashio K, Udagawa N, Takahashi N, Suda T: Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci USA 1998;95:3597-3602.
15. Anderson DM, Maraskovsky E, Billingsley WL, Dougall WC, Tometsko ME, Roux ER, Teepe MC, DuBose RF, Cosman D, Galibert L: A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function. Nature 1997;390:175-179.
16. Wong BR, Rho J, Arron J, Robinson E, Orlinick J, Chao M, Kalachikov S, Cayani E, Bartlett FS 3rd, Frankel WN, Lee SY, Choi Y: TRANCE is a novel ligand of the tumor necrosis factor receptor family that activates c-Jun N-terminal kinase in T cells. J Biol Chein 1997;272:25190-25194.
17. Wong BR, Josien R, Choi Y: TRANCE is a TNF family member that regulates dendritic cell and osteoclast function. J Leukoc Biol 1999;6-5:715-724.
18. Fata JE, Kong YY, Li J, Sasaki T, Irie-Sasaki J, Moorehead RA, Elliott R, Scully S, Voura EB, Lacey DL, Boyle WJ, Khokha R, Penninger JM: The osteoclast differentiation factor osteoprotegerin-ligand is essential for mammary gland development. Cell 2000;103:41-50.
19. Li J, Peet GW, Pullen SS, Schembri-King J, Warren TC, Marcu KB, Kehry MR, Barton R, Jakes S: Recombinant I-kappa-B kinases alpha and beta are direct kinases of I-kappa-B-alpha. J Biol Chem 1998 ;273:30736-30741.
20. Suda T, Takahashi N, Udagawa N, Jimi E, Gillespie MT, Martin TJ: Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families. Endocr Rel, 1999;20:345-357.
21. Feng X: Regulatory roles and molecular signaling of TNF family members in osteoclasts. Gene 2005;350:1-13.
22. Kong YY, Yoshida H, Sarosi I, Tan HL, Timms E, Capparelli C, Morony S, Oliveira-dos-Santos AJ, Van G, Itie A, Khoo W, Wakeham A, Dunstan CR, Lacey DL, Mak TW, Boyle WJ, Penninger JM: OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymphnode organogenesis. Nature 1999;397:315-323.
23. Dougall WC, Glaccum M, Charrier K, Rohrbach K, Brasel K, De Smedt T, Daro E, Smith J, Tometsko ME, Maliszewski CR, Armstrong A, Shen V, Bain S, Cosman D, Anderson D, Morrissey PJ, Peschon JJ, Schuh J: RANK is essential for osteoclast and lymph node development. Genes Dev 1999;13:2412-2424.
24. Li J, Sarosi I, Yan X-Q, Morony S, Capparelli C, Tan HL, McCabe S, Elliott R, Scully S, Van G, Kaufman S, Juan SC, Sun Y, Tarpley J, Martin L, Christensen K, McCabe J, Kostenuik P, Hsu H, Fletcher F, Dunstan CR, Lacey DL, Boyle WJ: RANK is the intrinsic hematopoietic cell surface receptor that controls osteoclastogenesis and regulation of bone mass and calcium metabolism. Proc Natl Acad Sci USA 2000;197:1566-1571.
25. Bucay N, Sarosi I, Dunstan CR, Morony S, Tarpley J, Capparelli C, Scully S, Tan HL, Xu W, Lacey DL, Boyle WJ, Simonet WS: Osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification. Genes Dev 1998;12:1260-1268.
26. Simonet WS, Lacey DL, Dunstan CR, Kelley M, Chang MS, Luthy R, Nguyen HQ, Wooden S, Bennett L, Boone T, Shimamoto G, DeRose M, Elliott R, Colombero A, Tan HL, Trail G, Sullivan J, Davy E, Bucay N, Renshaw-Gegg L, Hughes TM, Hill D, Pattison W, Campbell P, Sander S, Van G, Tarpley J, Derby P, Lee R, Boyle WJ: Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 1997;89:309-319.
27. Burgess TL, Qian Y, Kaufman S, Ring BD, Van G, Capparelli C, Kelley M, Hsu H, Boyle WJ, Dunstan CR, Hu S, Lacey DL: The ligand for osteoprotegerin (OPGL) directly activates mature osteoclasts. J Cell Biol 1999;145:527-538.
28. Fuller K, Wong B, Fox S, Choi Y, Chambers TJ: TRANCE is necessary and sufficient for osteoblast-mediated activation of bone resorption in osteoclasts. J Exp Med 1998;188:997-1001.
29. Lum L, Wong BR, Josien R, Becherer JD, Erdjument-Bromage H, Schlondorff J, Tempst P, Choi Y, Blobel CP: Evidence for a role of a tumor necrosis factor-alpha (TNF-alpha)-converting enzyme-like protease in shedding of TRANCE, a TNT family member involved in osteoclasto-genesis and dendritic cell survival. J Biol Chem 1999;274:13613-13618.
30. Wong BR, Besser D, Kim N, Arron JR, Vologodskaia M, Hanafusa H, Choi Y: TRANCE, a TNF family member, activates Akt/PKB through a signaling complex involving TRAF6 and c-Src. Mol Cell 1999;4:1041-1049.
31. Wong BR, Josien R, Lee SY, Sauter B, Li HL, Steinman RM, Choi Y: TRANCE (tumor necrosis factor [TNF]-related activation-induced cytokine), a new TNF family member predominantly expressed in T cells, is a dendritic cell-specific survival factor. J Exp Med 1997;186:2075-2080.
32. Doggrell SA: Present and future pharmacotherapy for osteoporosis. Drugs Today (Bare) 2003;139:633-657.
33. Zhang J, Dai J, Yao Z, Lu Y, Dougall W, Keller ET: Soluble receptor activator of nuclear factor kappaB Fc diminishes prostate cancer progression in bone. Cancer Res 2003;63:7883-7890.
34. Bekker PJ, Holloway DL, Rasmussen AS, Murphy R, Martin SW, Leese PT, Holmes GB, Dunstan CR, DePaoli AM: A single-dose placebo-controlled study of AMG 162, a fully human monoclonal antibody to RANKL, in postmenopausal women. J Bone Miner Res 2004;19:1059-1066.
35. Hsu H, Lacey DL, Dunstan CR, Solovyev I, Colombero A, Timms E, Tan HL, Elliott G, Kelley MJ, Sarosi I, Wang L, Xia XZ, Elliott R, Chiu L, Black T, Scully S, Capparelli C, Morony S, Shimamoto G, Bass MB, Boyle WJ: Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand. Proc Natl Acad Sci U S A 1999;96:3540-3545.
36. Locksley RM, Killeen N, Lenardo MJ: The TNF and TNF receptor superfamilies: integrating mammalian biology. Cell 2001;104:487-501.
37. Chung JY, Park YC, Ye H, Wu H: All TRAFs are not created equal: common and distinct molecular mechanisms of TRAF-mediated signal transduction. J Cell Sci 2002;1115:679-688.
38. Darnay BG, Haridas V, Ni J, Moore PA, Agaarwal BB: Characterization of the intracellular domain of receptor activator of NF-kappaB (RANK). Interaction with tumor necrosis factor receptor-associated factors and activation of NF-kappaB and c-Jun N-terminal kinase. J Biol Chem 1998;273:20551-20555.
39. Wong BR, Josien R, Lee SY, Vologodskaia M, Steinman RM, Choi Y: The TRAF family of signal transducers mediates NF-kappa-B activation by the TRANCE receptor. J Biol Chem 1998;273:28355-28359.
40. Kim HH, Lee DE, Shin JN, Lee YS, Jeon YM, Chung CH, Ni J, Kwon BS, Lee ZH: Receptor activator of NF-kappaB recruits multiple TRAF family adaptors and activates c-Jun N-terminal kinase. FEBS Lett 1999;443:297-302.
41. Darnay BG, Ni J, Moore PA, Aggarwal BB: Activation of NF-kappaB by RANK requires tumor necrosis factor receptor-associated factor (TRAF) 6 and NF-kappaB-inducing kinase. Identification of a novel TRAF6 interaction motif. J Biol Chem 1999;274:7724-7731.
42. Galibert L, Tometsko ME, Anderson DM, Cosman D, Dougall WC: The involvement of multiple tumor necrosis factor receptor (TNFR)-associated factors in the signaling mechanisms of receptor activator of NF-kappaB, a member of the TNFR superfamily. J Biol Chem 1998;273:34120-34127.
43. Armstrong AP, Tometsko ME, Glaccum M, Sutherland CL, Cosman D, Dougall WC: A RANK/TRAF6-dependent signal transduction pathway is essential for osteoclast cytoskeletal organization and resorptive function. J Biol Chem 2002;277:44347-44356.
44. Liu W, Xu D, Yang H, Xu H, Shi Z, Cao X, Takeshita S, Liu J, Teale M, Feng X: Functional identification of three RANK cytoplasmic motifs mediating osteoclast differentiation and function. J Biol Chem 2004;279:54759-54769.
45. Liu W, Wang S, Wei S, Sun L, Feng X: RANK cytoplasmic motif, PFQEP369-373, plays a predominant role in osteoclast survival in part by activating Akt/PK13 and its downstream effector AFX/FOXO4. J Biol Chem 2005;280:43064-43072.
46. Ye H, Arron JR, Lamothe B, Cirilli M, Kobayashi T, Shevde NK, Segal D, Dzivenu OK, Vologodskaia M, Yim M, Du K, Singh S, Pike JW, Darnay BG, Choi Y, Wu H: Distinct molecular mechanism for initiating TRAF6 signalling. Nature 2002;418:443-447.
47. Mizukami J, Takaesu G, Akatsuka H, Sakurai H, Ninomiya-Tsuji J, Matsumoto K, Sakurai N: Receptor activator of NF-kappaB ligand (RANKL) activates TAK1 mitogen-activated protein kinase kinase kinase through a signaling complex containing RANK, TAB2, and TRAF6. Mol Cell Biol 2002;22:992-1000.
48. Ninomiya-Tsuji J, Kishimoto K, Hiyama A, Inoue J, Cao Z, Matsumoto K: The kinase TAK1 can activate the NIK-I kappaB as well as the MAP kinase cascade in the IL-I signalling pathway. Nature 1999;1398:252-256.
49. Sbirakabe K, Yamaguchi K, Shibuya H, Irie K, Matsuda S, Moriguchi T, Gotoh Y, Matsumoto K, Nishida E: TAK 1 mediates the ceramide signaling to stress-activated protein kinase/c-Jun N-terminal kinase. J Biol Chem 1997;272:8141-8144.
50. Lee SW, Han SI, Kim HH, Lee ZH: TAK1-dependent activation of AP-1 and c-Jun N-terminal kinase by receptor activator of NF-kappaB. J Biochem Mol Biol 2002;35:371-376.
51. Ge B, Gram H, Di Padova F, Huang B, New L, Ulevitch RJ, Luo Y, Han J: MAPKK-independent activation of p38alpha mediated by TA1B-dependent autophosphorylation of p38alpha. Science 2002;295:1291-1294.
52. Takayanagi H, Kim S, Koga T, Nishina H, Isshiki M, Yoshida H, Saiura A, Isobe M, Yokochi T, Inoue J, Wagner EF, Mak TW, Kodama T, Taniguchi T: Induction and activation of the transcription factor NFATc1 (NFAT2) integrate RANKL signaling in terminal differentiation of osteoclasts. Dev Cell 2002;3:889-901.
53. Ishida N, Hayashi K, Hoshijima M, Ogawa T, Koga S, Miyatake Y, Kumegawa M, Kimura T, Takeya T: Large scale gene expression analysis of osteoclastogenesis in vitro and elucidation of NFAT2 as a key regulator. J Biol Chem 2002;277:41147-41156.
54. Takayanagi H, Kim S, Matsuo, K, Suzuki H, Suzuki T, Sato K, Yokochi T, Oda H, Nakamura K, Ida N, Wagner EF, Taniguchi T: RANKL maintains bone homeostasis through c-Fos-dependent induction of interferon-beta. Nature 2002;416:744-749.
55. Kobayashi T, Walsh PT, Walsh MC, Speirs KM, Chiffoleau E, King CG, Hancock WW, Caamano JH, Hunter CA, Scott P, Turka LA, Choi Y: TRAF6 is a critical factor for dendritic cell maturation and development. Immunity 2003;19:353-363.
56. He MM, Smith AS, Oslob JD, Flanagan WM, Braisted AC, Whitty A, Cancilla MT, Wang J, Lugovskoy AA, Yoburn JC, Fung AD, Farrington G, Eldredge JK, Day ES, Cruz LA, Cachero TG, Miller SK, Friedman JE, Choong IC, Cunningham BC: Small-molecule inhibition of TNF-alpha. Science 2005;310:1022-1025.
57. Xu D, Shi Z, McDonald J, Pan G, Cao X, Yu X, Feng X: Development of a chimaeric receptor approach to study signalling by tumour necrosis factor receptor family members. Biochem J 2004;383:219-225.
58. Yonehara S, Ishii A, Yonehara M: A cell-killing monoclonal antibody (anti-Fas) to a cell surface antigen codownregulated with the receptor of tumor necrosis factor. J Exp Med 1989;169:1747-1756.
59. Itoh N, Yonehara S, Ishii A, Yonehara M, Mizushima S, Sameshima M, Hase A, Seto Y, Nagata S: The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis. Cell 1991;66:233-243.
60. Shui C, Riggs BL, Khosla S: The immunosuppressant rapamycin, alone or with transforming growth factor-beta, enhances osteoclast differentiation of RAW264.7 monocyte-macrophage cells in the presence of RANK-ligand. Calcif Tissue Int 2002;71:437-446.
61. Battaglino R, Kim D, Fu B, Fu XY, Stashenko P: c-Myc is required for osteoclast differentiation. J Bone Miner Res 2002;17:763-773.