Selective inhibition of RANK blocks osteoclast maturation and function and prevents bone loss in mice

Journal of Clinical Investigation

Volumn 119, Issue 4, 2009, Pages 813-825

  Kim, Hyunsoo ^a,b   Han, Kyoung Choi ^a   Ji, Hye Shin ^a   Kyung, Hee Kim ^a   Ji, Young Huh ^a   Seung, Ah Lee ^a   Ko, Chang Yong ^c   Kim, Han Sung ^c   Shin, Hong In ^d   Hwa, Jeong Lee ^a   Jeong, Daewon ^e   Kim, Nacksung ^f   Choi, Yongwon ^g   Soo, Young Lee ^a  

^a Ewha Womans University   (South Korea)

^b Gyeongsang National University   (South Korea)

^c Yonsei University Wonju   (South Korea)

^d Kyungpook National University   (South Korea)

^e Yeungnam University College of Medicine   (South Korea)

^f Chonnam National University Medical School   (South Korea)

^g UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACTIN; OSTEOCLAST DIFFERENTIATION FACTOR; PROTEIN CDC42; PROTEIN INHIBITOR; RAC1 PROTEIN; RANK RECEPTOR INHIBITOR; RECEPTOR ACTIVATOR OF NUCLEAR FACTOR KAPPA B; UNCLASSIFIED DRUG; VAV PROTEIN; MONOMERIC GUANINE NUCLEOTIDE BINDING PROTEIN; OLIGOPEPTIDE; RECOMBINANT PROTEIN; TNFRSF11A PROTEIN, MOUSE; TUMOR NECROSIS FACTOR RECEPTOR ASSOCIATED FACTOR 6; VAV3 PROTEIN, MOUSE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; APOPTOSIS; ARTICLE; BONE DESTRUCTION; BONE MARROW CELL; CELL DIFFERENTIATION; CELL DISRUPTION; CELL FUNCTION; CELL MATURATION; CELL STRAIN HEK293; CONTROLLED STUDY; DISEASE MODEL; DRUG EFFECT; DRUG INHIBITION; DRUG MECHANISM; EMBRYO; HUMAN; HUMAN CELL; INFLAMMATION; MACROPHAGE; MOUSE; NONHUMAN; OSTEOCLAST; OSTEOLYSIS; OSTEOPOROSIS; OVARIECTOMY; PRIORITY JOURNAL; PROTEIN MOTIF; PROTEIN TARGETING; SIGNAL TRANSDUCTION; TREATMENT OUTCOME; AMINO ACID SEQUENCE; ANIMAL; C57BL MOUSE; CYTOLOGY; DRUG ANTAGONISM; FEMALE; GENETIC TRANSDUCTION; GENETICS; METABOLISM; PATHOLOGY; PATHOPHYSIOLOGY; PHYSIOLOGY; SITE DIRECTED MUTAGENESIS;

AMINO ACID MOTIFS; AMINO ACID SEQUENCE; ANIMALS; BONE RESORPTION; FEMALE; MICE; MICE, INBRED C57BL; MONOMERIC GTP-BINDING PROTEINS; MUTAGENESIS, SITE-DIRECTED; OLIGOPEPTIDES; OSTEOCLASTS; PROTO-ONCOGENE PROTEINS C-VAV; RECEPTOR ACTIVATOR OF NUCLEAR FACTOR-KAPPA B; RECOMBINANT PROTEINS; SIGNAL TRANSDUCTION; TNF RECEPTOR-ASSOCIATED FACTOR 6; TRANSDUCTION, GENETIC;

EID: 65249180600     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI36809     Document Type: Article

References (57)

1. Zaidi, M. 2007. Skeletal remodeling in health and disease. Nat. Med. 13:791-801.
2. Mundy, G.R. 2007. Osteoporosis and inflammation. Nutr. Rev. 65:S147-S151.
3. Aoki, K., et al. 2006. A TNF receptor loop peptide mimic blocks RANK ligand-induced signaling, bone resorption, and bone loss. J. Clin. Invest. 116:1525-1534.
4. Takayanagi, H. 2007. Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems. Nat. Rev. Immunol. 7:292-304.
5. Walsh, M.C., et al. 2006. Osteoimmunology: interplay between the immune system and bone metabolism. Annu. Rev. Immunol. 24:33-63.
6. Boyce, B.F., Schwarz, E.M., and Xing, L. 2006. Osteoclast precursors: cytokine-stimulated immunomodulators of inflammatory bone disease. Curr. Opin. Rheumatol. 18:427-432.
7. Boyle, W.J., Simonet, W.S., and Lacey, D.L. 2003. Osteoclast differentiation and activation. Nature. 423:337-342.
8. Suda, T. 1999. Modulation of osteoclast differentiation and function by the new member of the tumor necrosis factor receptor and ligand families. Endocr. Rev. 20:345-357.
9. Wong, B.R., et al. 1998. The TRAF family of signal transducers mediates NF-κB activation by the TRANCE receptor. J. Biol. Chem. 273:28355-28359.
10. Asagiri, M., and Takayanagi, H. 2007. The molecular understanding of osteoclast differentiation. Bone. 40:251-264.
11. Lomaga, M.A., et al. 1999. TRAF6 deficiency results in osteopetrosis and defective interleukin-1, CD40, and LPS signaling. Genes Dev. 13:1015-1024.
12. Naito, A., et al. 1999. Severe osteopetrosis, defective interleukin-1 signalling and lymph node organogenesis in TRAF6-deficient mice. Genes Cells. 4:353-362.
13. Theill, L.E., Boyle, W.J., and Penninger, J.M. 2002. RANK-L and RANK: T cells, bone loss, and mammalian evolution. Annu. Rev. Immunol. 20:795-823.
14. Walsh, M.C., and Choi, Y. 2003. Biology of the TRANCE axis. Cytokine Growth Factor Rev. 14:251-263.
15. Takayanagi, H. 2005. Mechanistic insight into osteoclast differentiation in osteoimmunology. J. Mol. Med. 83:170-179.
16. Takayanagi, H. 2002. Induction and activation of the transcription factor NFATc1 (NFAT2) integrate RANKL signaling in terminal differentiation of osteoclasts. Dev. Cell. 3:889-901.
17. Asagiri, M., et al. 2005. Autoamplification of NFATc1 expression determines its essential role in bone homeostasis. J. Exp. Med. 202:1261-1269.
18. Crotti, T.N., et al. 2006. NFATc1 regulation of the human β3 integrin promoter in osteoclast differentiation. Gene. 372:92-102.
19. Kim, Y., et al. 2005. Contribution of NFATc1 to the transcriptional control of immunoreceptor osteoclast-associated receptor but not triggering receptor expressed by myeloid cells-2 during osteoclastogenesis. J. Biol. Chem. 280:32905-32913.
20. Matsumoto, M., et al. 2004. Essential role of p38 mitogen-activated protein kinase in cathepsin K gene expression during osteoclastogenesis through association of NFATc1 and PU.1. J. Biol. Chem. 279:45969-45979.
21. Koga, T., et al. 2004. Costimulatory signals mediated by the ITAM motif cooperate with RANKL for bone homeostasis. Nature. 428:758-763.
22. Tanaka, S. 2007. Signaling axis in osteoclast biology and therapeutic targeting in the RANKL/ RANK/OPG system. Am. J. Nephrol. 27:466-478.
23. Josien, R., et al. 2000. TRANCE, a tumor necrosis factor family member, enhances the longevity and adjuvant properties of dendritic cells in vivo. J. Exp. Med. 191:495-502.
24. Loser, K., et al. 2006. Epidermal RANKL controls regulatory T-cell numbers via activation of dendritic cells. Nat. Med. 12:1372-1379.
25. Fata, J.E., et al. 2000. The osteoclast differentiation factor osteoprotegerin-ligand is essential for mammary gland development. Cell. 103:41-50.
26. Sipos, W., Pietschmann, P., and Rauner, M. 2008. Strategies for novel therapeutic approaches targeting cytokines and signaling pathways of osteoclasto-and osteoblastogenesis in the fight against immune-mediated bone and joint diseases. Curr. Med. Chem. 15:127-136.
27. Xu, D., Wang, S., Liu, W., and Feng, X. 2006. A novel receptor activator of NF-κB (RANK) cytoplasmic motif plays an essential role in osteoclastogenesis by committing macrophages to the osteoclast lineage. J. Biol. Chem. 281:4678-4690.
28. Kadono, Y., et al. 2005. Strength of TRAF6 signalling determines osteoclastogenesis. EMBO Rep. 6:171-176.
29. Choi, J.M., et al. 2006. Intranasal delivery of the cytoplasmic domain of CTLA-4 using a novel protein transduction domain prevents allergic inflammation. Nat. Med. 12:574-579.
30. Takayanagi, H., et al. 2002. RANKL maintains bone homeostasis through c-Fos-dependent induction of interferon-β. Nature. 416:744-749.
31. Soriano, P., Montgomery, C., Geske, R., and Bradley, A. 1991. Targeted disruption of the c-src proto-oncogene leads to osteopetrosis in mice. Cell. 64:693-702.
32. Takayanagi, H., et al. 2000. T-cell-mediated regulation of osteoclastogenesis by signalling cross-talk between RANKL and IFN-γ. Nature. 408:600-605.
33. McHugh, K.P., et al. 2000. Mice lacking β3 integrins are osteosclerotic because of dysfunctional osteoclasts. J. Clin. Invest. 105:433-440.
34. Razzouk, S., Lieberherr, M., and Cournot, G. 1999. Rac-GTPase, OC cytoskeleton and bone resorption. Eur. J. Cell Biol. 78:249-255.
35. Faccio, R., et al. 2005. Vav3 regulates osteoclast function and bone mass. Nat. Med. 11:284-290.
36. Abu-Amer, Y., Ross, F.P., Edwards, J., and Teitelbaum, S.L. 1999. Lipopolysaccharide-stimulated osteoclastogenesis is mediated by tumor necrosis factor via its P55 receptor. J. Clin. Invest. 100:1557-1565.
37. Lam, J., et al. 2000. TNF-α induces osteoclastogenesis by direct stimulation of macrophages exposed to permissive levels of RANK ligand. J. Clin. Invest. 106:1481-1488.
38. Ochi, S., et al. 2007. Pathological role of osteoclast costimulation in arthritis-induced bone loss. Proc. Natl. Acad. Sci. U. S. A. 104:11394-11399.
39. Josien, R., et al. 1999. TRANCE, a TNF family member, is differentially expressed on T cell subsets and induces cytokine production in dendritic cells. J. Immunol. 162:2562-2568.
40. Wong, B.R., et al. 1997. 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. 186:2075-2080.
41. Ouaaz, F., et al. 2002. Dendritic cell development and survival require distinct NF-kappaB subunits. Immunity. 16:257-270.
42. Yagi, M., et al. 2005. DC-STAMP is essential for cell-cell fusion in osteoclasts and foreign body giant cells. J. Exp. Med. 202:345-351.
43. Lee, S.H., et al. 2006. v-ATPase V0 subunit d2-deficient mice exhibit impaired OC fusion and increased bone formation. Nat. Med. 12:1403-1409.
44. Cui, W., et al. 2007. CD200 and its receptor, CD200R, modulate bone mass via the differentiation of osteoclasts. Proc. Natl. Acad. Sci. U. S. A. 104:14436-14441.
45. Burgess, T.L., et al. 1999. The ligand for osteoprotegerin (OPGL) directly activates mature osteoclasts. J. Cell Biol. 145:527-538.
46. Vaananen, H.K., Zao, H., Mulari, M., and Halleen, J.M. 2000. The cell biology of osteoclast function. J. Cell Sci. 113:377-381.
47. Amstrong, A.P., et al. 2002. A RANK/TRAF6-dependent signal transduction pathway is essential for osteoclast cytoskeletal organization and resorptive function. J. Biol. Chem. 277:44347-44356.
48. Boyce, B.F., and Xing, L. 2007. Biology of RANK, RANKL, and osteoprotegerin. Arthritis Res. Ther. 9(Suppl. 1):S1.
49. Cohen, S. 2006. Role of RANK ligand in normal and pathological bone remodeling and the therapeutic potential of novel inhibitory molecules in musculoskeletal diseases. Arthritis Rheum. 55:15-18.
50. Inoue, J., Gohda, J., and Akiyama, T. 2007. Characteristics and biological functions of TRAF6. Adv. Exp. Med. Biol. 597:72-79.
51. Jimi, E., et al. 2004. Selective inhibition of NF-κB blocks osteoclastogenesis and prevents inflammatory bone destruction in vivo. Nat. Med. 10:617-624.
52. Verma, I.M. 2004. Nuclear factor (NF)-κB proteins: therapeutic targets. Ann. Rheum. Dis. 63(Suppl. 2):ii57-ii61.
53. Koga, T., et al. 2005. NFAT and Osterix cooperatively regulate bone formation. Nat. Med. 11:880-885.
54. Suda, T., Jimi, E., Nakamura, I., and Takahashi, N. 1997. Role of 1 α,25-dihydroxyvitamin D3 in osteoclast differentiation and function. Methods Enzymol. 282:223-235.
55. Takami, M., Woo, J.T., and Nagai, K. 1999. Osteoblastic cells induce fusion and activation of osteoclasts through a mechanism of macrophage-colony- stimulating factor production. Cell Tissue Res. 298:327-334.
56. Lee, S.K., et al. 2006. Interleukin-7 influences osteoclast function in vivo but is not a critical factor in ovariectomy-induced bone loss. J. Bone Miner. Res. 21:695-702.
57. Montero, A., et al. 2000. Disruption of the fibroblast growth factor-2 gene results in decreased bone mass and bone formation. J. Clin. Invest. 105:1085-1093.