NFATc1 in mice represses osteoprotegerin during osteoclastogenesis and dissociates systemic osteopenia from inflammation in cherubism

Journal of Clinical Investigation

Volumn 118, Issue 11, 2008, Pages 3775-3789

  Aliprantis, Antonios O ^a,b   Ueki, Yasuyoshi ^c,f   Sulyanto, Rosalyn ^a,d   Park, Arnold ^a   Sigrist, Kirsten S ^a   Sharma, Sudarshana M ^e   Ostrowski, Michael C ^e   Olsen, Bjorn R ^c   Glimcher, Laurie H ^a,b  

^a HARVARD SCHOOL OF PUBLIC HEALTH   (United States)

^b BRIGHAM AND WOMEN S HOSPITAL   (United States)

^c Department of Developmental Biology ^*  (United States)

^d HARVARD SCHOOL OF DENTAL MEDICINE   (United States)

^e OHIO STATE UNIVERSITY   (United States)

^f UNIVERSITY OF MISSOURI KANSAS CITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

OSTEOCLAST DIFFERENTIATION FACTOR; OSTEOPROTEGERIN; TRANSCRIPTION FACTOR NFAT; TRANSCRIPTOME;

ALBERS SCHOENBERG DISEASE; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BONE REMODELING; CONTROLLED STUDY; FIBROUS DYSPLASIA; GENE DELETION; GENE EXPRESSION; INFLAMMATION; MOUSE; NONHUMAN; OSTEOCLAST; OSTEOLYSIS; OSTEOPENIA; OSTEOPOROSIS; PRIORITY JOURNAL;

ANIMALS; BONE DISEASES, METABOLIC; CHERUBISM; INFLAMMATION; MICE; MICE, KNOCKOUT; MICE, TRANSGENIC; NFATC TRANSCRIPTION FACTORS; OSTEOCLASTS; OSTEOPROTEGERIN;

EID: 55849088412     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI35711     Document Type: Article

References (78)

1. United States Department of Health and Human Services. 2004. Bone health and osteoporosis: a report of the Surgeon General. http://www.surgeongeneral. gov/library/bonehealth/content.html.
2. Woolf, A.D., and Pfleger, B. 2003. Burden of major musculoskeletal conditions. Bull. World Health Organ. 81:646-656.
3. Ueki, Y., et al. 2007. Increased myeloid cell responses to M-CSF and RANKL cause bone loss and inflammation in SH3BP2 "cherubism" mice. Cell. 128:71-83.
4. Goldring, S.R., and Gravallese, E.M. 2000. Pathogenesis of bone erosions in rheumatoid arthritis. Curr. Opin. Rheumatol. 12:195-199.
5. Wada, T., Nakashima, T., Hiroshi, N., and Penninger, J.M. 2006. RANKL-RANK signaling in osteoclastogenesis and bone disease. Trends Mol. Med. 12:17-25.
6. Teitelbaum, S.L., and Ross, F.P. 2003. Genetic regulation of osteoclast development and function. Nat. Rev. Genet. 4:638-649.
7. Simonet, W.S., et al. 1997. Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell. 89:309-319.
8. Bucay, N., et al. 1998. Osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification. Genes Dev. 12:1260-1268.
9. Boyce, B.F., and Xing, L. 2007. Biology of RANK, RANKL, and osteoprotegerin. Arthritis Res. Ther. 9(Suppl. 1):S1.
10. Hogan, P.G., Chen, L., Nardone, J., and Rao, A. 2003. Transcriptional regulation by calcium, calcineurin, and NFAT. Genes Dev. 17:2205-2232.
11. Graef, I.A., Chen, F., and Crabtree, G.R. 2001. NFAT signaling in vertebrate development. Curr. Opin. Genet. Dev. 11:505-512.
12. Horsley, V., Aliprantis, A.O., Polak, L., Glimcher, L.H., and Fuchs, E. 2008. NFATc1 balances quiescence and proliferation of skin stem cells. Cell. 132:299-310.
13. Ishida, N., et al. 2002. Large scale gene expression analysis of osteoclastogenesis in vitro and elucidation of NFAT2 as a key regulator. J. Biol. Chem. 277:41147-41156.
14. Takayanagi, 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.
15. Kim, K., Lee, S.H., Ha Kim, J., Choi, Y., and Kim, N. 2008. NFATc1 induces osteoclast fusion via up-regulation of Atp6v0d2 and the dendritic cell-specific transmembrane protein (DC-STAMP). Mol. Endocrinol. 22:176-185.
16. Sharma, S.M., et al. 2007. MITF and PU.1 recruit p38 MAPK and NFATc1 to target genes during osteoclast differentiation. J. Biol. Chem. 282:15921-15929.
17. Kim, Y., et al. 2005. Contribution of nuclear factor of activated T cells c1 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.
18. Crotti, T.N., et al. 2008. PU.1 and NFATc1 mediate osteoclastic induction of the mouse beta3 integrin promoter. J. Cell. Physiol. 215:636-644.
19. Sharma, S.M., et al. 2006. Genetics and genomics of osteoclast differentiation: integrating cell signaling pathways and gene networks. Crit. Rev. Eukaryot. Gene Expr. 16:253-277.
20. Ranger, A.M., et al. 1998. The transcription factor NF-ATc is essential for cardiac valve formation. Nature. 392:186-190.
21. Luis de la Pompa, J., et al. 1998. Role of the NF-ATc transcription factor in morphogenesis of cardiac valves and septum. Nature. 392:182-186.
22. Asagiri, M., et al. 2005. Autoamplification of NFATc1 expression determines its essential role in bone homeostasis. J. Exp. Med. 202:1261-1269.
23. Winslow, M.M., et al. 2006. Calcineurin/NFAT signaling in osteoblasts regulates bone mass. Dev. Cell. 10:771-782.
24. Liu, B., Yu, S.F., and Li, T.J. 2003. Multinucleated giant cells in various forms of giant cell containing lesions of the jaws express features of osteoclasts. J. Oral Pathol. Med. 32:367-375.
25. Ueki, Y., et al. 2001. Mutations in the gene encoding c-Abl-binding protein SH3BP2 cause cherubism. Nat. Genet. 28:125-126.
26. Tiziani, V., et al. 1999. The gene for cherubism maps to chromosome 4p16. Am. J. Hum. Genet. 65:158-166.
27. Lietman, S.A., Kalinchinko, N., Deng, X., Kohanski, R., and Levine, M.A. 2006. Identification of a novel mutation of SH3BP2 in cherubism and demonstration that SH3BP2 mutations lead to increased NFAT activation. Hum. Mutat. 27:717-718.
28. Weitzmann, M.N., and Pacifici, R. 2005. The role of T lymphocytes in bone metabolism. Immunol. Rev. 208:154-168.
29. Peng, S.L., Gerth, A.J., Ranger, A.M., and Glimcher, L.H. 2001. NFATc1 and NFATc2 together control both T and B cell activation and differentiation. Immunity. 14:13-20.
30. Kaminuma, O., et al. 2008. Differential contribution of NFATc2 and NFATc1 to TNF-alpha gene expression in T cells. J. Immunol. 180:319-326.
31. Kuhn, R., and Torres, R.M. 2002. Cre/loxP recombination system and gene targeting. Methods Mol. Biol. 180:175-204.
32. Kuhn, R., Schwenk, F., Aguet, M., and Rajewsky, K. 1995. Inducible gene targeting in mice. Science. 269:1427-1429.
33. Rodda, S.J., and McMahon, A.P. 2006. Distinct roles for Hedgehog and canonical Wnt signaling in specification, differentiation and maintenance of osteoblast progenitors. Development. 133:3231-3244.
34. Kawata, T., et al. 1999. Recruitment of osteoclasts in the mandibular condyle of growing osteopetrotic (op/op) mice after a single injection of macrophage colony-stimulating factor. Arch. Oral Biol. 44:81-88.
35. Tolar, J., Teitelbaum, S.L., and Orchard, P.J. 2004. Osteopetrosis. N. Engl. J. Med. 351:2839-2849.
36. Jacquin, C., Gran, D.E., Lee, S.K., Lorenzo, J.A., and Aguila, H.L. 2006. Identification of multiple osteoclast precursor populations in murine bone marrow. J. Bone Miner. Res. 21:67-77.
37. Leenen, P.J., de Bruijn, M.F., Voerman, J.S., Campbell, P.A., and van Ewijk, W. 1994. Markers of mouse macrophage development detected by monoclonal antibodies. J. Immunol. Methods. 174:5-19.
38. Clausen, B.E., Burkhardt, C., Reith, W., Renkawitz, R., and Forster, I. 1999. Conditional gene targeting in macrophages and granulocytes using LysMcre mice. Transgenic Res. 8:265-277.
39. Kenner, L., et al. 2004. Mice lacking JunB are osteopenic due to cell-autonomous osteoblast and osteoclast defects. J. Cell Biol. 164:613-623.
40. Kim, H.J., et al. 2006. Glucocorticoids suppress bone formation via the osteoclast. J. Clin. Invest. 116:2152-2160.
41. Kurihara, N., Tatsumi, J., Arai, F., Iwama, A., and Suda, T. 1998. Macrophage-stimulating protein (MSP) and its receptor, RON, stimulate human osteoclast activity but not proliferation: effect of MSP distinct from that of hepatocyte growth factor. Exp. Hematol. 26:1080-1085.
42. Sato, M., and Grasser, W. 1990. Myosin II antibodies inhibit the resorption activity of isolated rat osteoclasts. Cell. Motil. Cytoskeleton. 17:250-263.
43. Wu, H., et al. 2007. Down syndrome critical region-1 is a transcriptional target of nuclear factor of activated T cells-c1 within the endocardium during heart development. J. Biol. Chem. 282:30673-30679.
44. Sundaram, K., et al. 2007. RANK ligand signaling modulates the matrix metalloproteinase-9 gene expression during osteoclast differentiation. Exp. Cell Res. 313:168-178.
45. Sato, T., et al. 1997. Identification of the membrane-type matrix metalloproteinase MT1-MMP in osteoclasts. J. Cell Sci. 110:589-596.
46. Wu, H., Peisley, A., Graef, I.A., and Crabtree, G.R. 2007. NFAT signaling and the invention of vertebrates. Trends Cell Biol. 17:251-260.
47. Kieslinger, M., et al. 2005. EBF2 regulates osteoblast-dependent differentiation of osteoclasts. Dev. Cell. 9:757-767.
48. Atkins, G.J., et al. 2001. Osteoprotegerin inhibits osteoclast formation and bone resorbing activity in giant cell tumors of bone. Bone. 28:370-377.
49. Kim, N., et al. 2005. Osteoclast differentiation independent of the TRANCE-RANK-TRAF6 axis. J. Exp. Med. 202:589-595.
50. Ruocco, M.G., et al. 2005. I{kappa}B kinase (IKK){beta}, but not IKK{alpha}, is a critical mediator of osteoclast survival and is required for inflammation-induced bone loss. J. Exp. Med. 201:1677-1687.
51. Begg, S.K., et al. 1993. Delayed hematopoietic development in osteopetrotic (op/op) mice. J. Exp. Med. 177:237-242.
52. Kim, K., et al. 2005. Nuclear factor of activated T cells c1 induces osteoclast-associated receptor gene expression during tumor necrosis factor-related activation-induced cytokine-mediated osteoclastogenesis. J. Biol. Chem. 280:35209-35216.
53. Asagiri, M., and Takayanagi, H. 2007. The molecular understanding of osteoclast differentiation. Bone. 40:251-264.
54. Mizuno, A., et al. 1998. Severe osteoporosis in mice lacking osteoclastogenesis inhibitory factor/osteoprotegerin. Biochem. Biophys. Res Commun. 247:610-615.
55. Li, J., et al. 2000. RANK is the intrinsic hematopoietic cell surface receptor that controls osteoclastogenesis and regulation of bone mass and calcium metabolism. Proc. Natl. Acad. Sci. U. S. A. 97:1566-1571.
56. Yun, T.J., 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.
57. Schoppet, M., et al. 2007. Osteoprotegerin expression in dendritic cells increases with maturation and is NF-kappaB-dependent. J. Cell. Biochem. 100:1430-1439.
58. Naito, A., et al. 1999. Severe osteopetrosis, defective interleukin-1 signalling and lymph node organogenesis in TRAF6-deficient mice. Genes Cells. 4:353-362.
59. Gohda, J., et al. 2005. RANK-mediated amplification of TRAF6 signaling leads to NFATc1 induction during osteoclastogenesis. EMBO J. 24:790-799.
60. Baksh, S., et al. 2002. NFATc2-mediated repression of cyclin-dependent kinase 4 expression. Mol. Cell. 10:1071-1081.
61. Hodge, M.R., et al. 1996. Hyperproliferation and dysregulation of IL-4 expression in NF-ATp-deficient mice. Immunity. 4:397-405.
62. Tsytsykova, A.V., and Goldfeld, A.E. 2000. Nuclear factor of activated T cells transcription factor NFATp controls superantigen-induced lethal shock. J. Exp. Med. 192:581-586.
63. Pettit, A.R., et al. 2001. TRANCE/RANKL knockout mice are protected from bone erosion in a serum transfer model of arthritis. Am. J. Pathol. 159:1689-1699.
64. Redlich, K., et al. 2002. Osteoclasts are essential for TNF-alpha-mediated joint destruction. J. Clin. Invest. 110:1419-1427.
65. Xu, X., et al. 2001. Direct removal in the mouse of a floxed neo gene from a three-loxP conditional knockout allele by two novel approaches. Genesis. 30:1-6.
66. Xanthoudakis, S., et al. 1996. An enhanced immune response in mice lacking the transcription factor NFAT1. Science. 272:892-895.
67. Lugo-Villarino, G., Maldonado-Lopez, R., Possemato, R., Penaranda, C., and Glimcher, L.H. 2003. T-bet is required for optimal production of IFN-gamma and antigen-specific T cell activation by dendritic cells. Proc. Natl. Acad. Sci. U. S. A. 100:7749-7754.
68. Erlebacher, A., and Derynck, R. 1996. Increased expression of TGF-beta 2 in osteoblasts results in an osteoporosis-like phenotype. J. Cell Biol. 132:195-210.
69. Takahashi, N., Udagawa, N., Tanaka, S., and Suda, T. 2003. Generating murine osteoclasts from bone marrow. Methods Mol. Med. 80:129-144.
70. Fajardo, R.J., Muller, R., Ketcham, R.A., and Colbert, M. 2007. Nonhuman anthropoid primate femoral neck trabecular architecture and its relationship to locomotor mode. Anat. Rec. (Hoboken). 290:422-436.
71. McHugh, K.P., et al. 2000. Mice lacking beta3 integrins are osteosclerotic because of dysfunctional osteoclasts. J. Clin. Invest. 105:433-440.
72. Jones, D.C., et al. 2006. Regulation of adult bone mass by the zinc finger adapter protein Schnurri-3. Science. 312:1223-1227.
73. Janckila, A.J., Takahashi, K., Sun, S.Z., and Yam, L.T. 2001. Naphthol-ASBI phosphate as a preferred substrate for tartrate-resistant acid phosphatase isoform 5b. J. Bone Miner. Res. 16:788-793.
74. Smith, C.W., and Goldman, A.S. 1972. Effects of concanavalin A and pokeweed mitogen in vivo on mouse peritoneal macrophages. Exp. Cell Res. 73:394-398.
75. Loots, G., and Ovcharenko, I. 2007. ECRbase: database of evolutionary conserved regions, promoters, and transcription factor binding sites in vertebrate genomes. Bioinformatics. 23:122-124.
76. Glass, D.A., 2nd, et al. 2005. Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation. Dev. Cell. 8:751-764.
77. Hirotani, H., Tuohy, N.A., Woo, J.T., Stern, P.H., and Clipstone, N.A. 2004. The calcineurin/nuclear factor of activated T cells signaling pathway regulates osteoclastogenesis in RAW264.7 cells. J. Biol. Chem. 279:13984-13992.
78. Wang, X., and Seed, B. 2003. A PCR primer bank for quantitative gene expression analysis. Nucleic Acids Res. 31:e154.