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Inflammatory Cytokines

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Bone Resorption

Part of the book series: Topics in Bone Biology ((TBB,volume 2))

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References

  1. Abrahamsen B, Shalhoub V, Larson EK, Eriksen EF, Beck-Nielsen H, Marks SC, Jr. (2000) Cytokine RNA levels in transiliac bone biopsies from healthy early postmenopausal women. Bone 26:137–45.

    Article  PubMed  CAS  Google Scholar 

  2. Abu-Amer Y, Erdmann J, Alexopoulou L, Kollias G, Ross FP, Teitelbaum SL (2000) Tumor necrosis factor receptors types 1 and 2 differentially regulate osteoclastogenesis. J Biol Chem 275:27307–10.

    PubMed  CAS  Google Scholar 

  3. Adcock IM, Shirasaki H, Gelder CM, Peters MJ, Brown CR, Barnes PJ (1994) The effects of glucocorticoids on phorbol ester and cytokine stimulated transcription factor activation in human lung. Life Sci 55:1147–53.

    Article  PubMed  CAS  Google Scholar 

  4. An J, Ribeiro RC, Webb P, Gustafsson JA, Kushner PJ, Baxter JD, et al. (1999) Estradiol repression of tumor necrosis factor-α transcription requires estrogen receptor activation function-2 and is enhanced by coactivators. Proc Natl Acad Sci USA 96:15161–6.

    Article  PubMed  CAS  Google Scholar 

  5. Armbrecht HJ, Boltz MA, Christakos S, Bruns ME (1998) Capacity of 1,25-dihydroxyvitamin D to stimulate expression of calbindin D changes with age in the rat. Arch Biochem Biophys 352:159–64.

    Article  PubMed  CAS  Google Scholar 

  6. Atkins GJ, Haynes DR, Geary SM, Loric M, Crotti TN, Findlay DM (2000) Coordinated cytokine expression by stromal and hematopoietic cells during human osteoclast formation. Bone 26:653–61.

    Article  PubMed  CAS  Google Scholar 

  7. Aubin JE, Bonnelye E (2000) Osteoprotegerin and its ligand: a new paradigm for regulation of osteoclastogenesis and bone resorption. Osteoporos Int 11:905–13.

    Article  PubMed  CAS  Google Scholar 

  8. Azuma Y, Kaji K, Katogi R, Takeshita S, Kudo A (2000) Tumor necrosis factor-α induces differentiation of and bone resorption by osteoclasts. J Biol Chem 275:4858–64.

    PubMed  CAS  Google Scholar 

  9. Baker PJ, Dixon M, Evans RT, Dufour L, Johnson E, Roopenian DC (1999) CD4(+) T cells and the proin-flammatory cytokines gamma interferon and interleukin-6 contribute to alveolar bone loss in mice. Infect Immun 67:2804–9.

    PubMed  CAS  Google Scholar 

  10. Banerjee C, McCabe LR, Choi JY, Hiebert SW, Stein JL, Stein GS, et al. (1997) Runt homology domain proteins in osteoblast differentiation: AML3/CBFA1 is a major component of a bone-specific complex. J Cell Biochem 66:1–8.

    Article  PubMed  CAS  Google Scholar 

  11. 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 16:348–60.

    PubMed  CAS  Google Scholar 

  12. Bellido T, Huening M, Raval-Pandya M, Manolagas SC, Christakos S (2000) Calbindin-D28k is expressed in osteoblastic cells and suppresses their apoptosis by inhibiting caspase-3 activity. J Biol Chem 275:26328–32.

    Article  PubMed  CAS  Google Scholar 

  13. Benson MD, Aubin JE, Xiao G, Thomas PE, Franceschi RT (1999) Cloning of a 2.5kb murine bone sialoprotein promoter fragment and functional analysis of putative Osf2 binding sites. J Bone Min Res 14:396–405.

    CAS  Google Scholar 

  14. Beresford JN, Gallagher JA, Gowen M, Couch M, Poser J, Wood DD, et al. (1984) The effects of monocyte-conditioned medium and interleukin 1 on the synthesis of collagenous and non-collagenous proteins by mouse bone and human bone cells in vitro. Biochim Biophys Acta 801:58–65.

    PubMed  CAS  Google Scholar 

  15. Bertolini DR, Nedwin GE, Bringman TS, Smith DD, Mundy GR (1986) Stimulation of bone resorption and inhibition of bone formation in vitro by human tumour necrosis factors. Nature 319:516–18.

    Article  PubMed  CAS  Google Scholar 

  16. Birkenkamp KU, Tuyt LM, Lummen C, Wierenga AT, Kruijer W, Vellenga E (2000) The p38 MAP kinase inhibitor SB203580 enhances nuclear factor-kappa B transcriptional activity by a non-specific effect upon the ERK pathway. Br J Pharmacol 131:99–107.

    Article  PubMed  CAS  Google Scholar 

  17. Bodine PV, Vernon SK, Komm BS (1996) Establishment and hormonal regulation of a conditionally transformed preosteocytic cell line from adult human bone. Endocrinology 137:4592–604.

    Article  PubMed  CAS  Google Scholar 

  18. Boss JM, Jensen PE (2003) Transcriptional regulation of the MHC class II antigen presentation pathway. Curr Opin Immunol 15:105–11.

    Article  PubMed  CAS  Google Scholar 

  19. Boyce BF, Xing L, Franzoso G, Siebenlist U (1999) Required and nonessential functions of nuclear factor-kappa B in bone cells. Bone 25:137–9.

    Article  PubMed  CAS  Google Scholar 

  20. Boyle WJ, Simonet WS, Lacey DL (2003) Osteoclast differentiation and activation. Nature 423:337–42.

    Article  PubMed  CAS  Google Scholar 

  21. Bradford PG, Maglich JM, Kirkwood KL (2000) IL-1 beta increases type 1 inositol trisphosphate receptor expression and IL-6 secretory capacity in osteoblastic cell cultures. Mol Cell Biol Res Commun 3:73–5.

    PubMed  CAS  Google Scholar 

  22. Brandstrom H, Jonsson KB, Vidal O, Ljunghall S, Ohlsson C, Ljunggren O (1998) Tumor necrosis factor-α and-beta upregulate the levels of osteoprotegerin mRNA in human osteosarcoma MG-63 cells. Biochem Biophys Res Commun 248:454–7.

    Article  PubMed  CAS  Google Scholar 

  23. Brennan FM, Browne KA, Green PA, Jaspar JM, Maini RN, Feldmann M (1997) Reduction of serum matrix metalloproteinase 1 and matrix metalloproteinase 3 in rheumatoid arthritis patients following anti-tumour necrosis factor-α (cA2) therapy. Br J Rheumatol 36:643–50.

    Article  PubMed  CAS  Google Scholar 

  24. Brogan IJ, Murray IA, Cerillo G, Needham M, White A, Davis JR (1999) Interaction of glucocorticoid receptor isoforms with transcription factors AP-1 and Nf-κB: lack of effect of glucocorticoid receptor beta. Mol Cell Endocrinol 157:95–104.

    Article  PubMed  CAS  Google Scholar 

  25. Burns K, Clatworthy J, Martin L, Martinon F, Plumpton C, Maschera B, et al. (2000) Tollip, a new component of the IL-1RI pathway, links IRAK to the IL-1 receptor. Nat Cell Biol 2:346–51.

    PubMed  CAS  Google Scholar 

  26. Burow ME, Weldon CB, Tang Y, McLachlan JA, Beckman BS (2001) Oestrogen-mediated suppression of tumour necrosis factor α-induced apoptosis in MCF-7 cells: subversion of Bcl-2 by anti-oestrogens. J Steroid Biochem Mol Biol 78:409–18.

    Article  PubMed  CAS  Google Scholar 

  27. Caldenhoven E, Liden J, Wissink S, Van de Stolpe A, Raaijmakers J, Koenderman L, et al. (1995) Negative cross-talk between RelA and the glucocorticoid receptor: a possible mechanism for the antiinflammatory action of glucocorticoids. Mol Endocrinol 9:401–12.

    Article  PubMed  CAS  Google Scholar 

  28. Canalis E (1987) Effects of tumor necrosis factor on bone formation in vitro. Endocrinology. 121:1596–604.

    PubMed  CAS  Google Scholar 

  29. Cao Z, Xiong J, Takeuchi M, Kurama T, Goeddel DV (1996) TRAF6 is a signal transducer for interleukin-1. Nature 383:443–6.

    Article  PubMed  CAS  Google Scholar 

  30. Carpentier I, Beyaert R (1999) TRAF1 is a TNF inducible regulator of Nf-κB activation. FEBS Lett 460:246–50.

    Article  PubMed  CAS  Google Scholar 

  31. Catrina AI, Lampa J, Ernestam S, af Klint E, Bratt J, Klareskog L, et al. (2002) Anti-tumour necrosis factor (TNF)-_α therapy (etanercept) down-regulates serum matrix metalloproteinase (MMP)-3 and MMP-1 in rheumatoid arthritis. Rheumatology (Oxford) 41:484–9.

    Article  PubMed  CAS  Google Scholar 

  32. Cenci S, Toraldo G, Weitzmann MN, Roggia C, Gao Y, Qian WP, et al. (2003) Estrogen deficiency induces bone loss by increasing T cell proliferation and lifespan through IFN-gamma-induced class II transactivator. Proc Natl Acad Sci USA 100:10405–10.

    Article  PubMed  CAS  Google Scholar 

  33. Cenci S, Weitzmann MN, Roggia C, Namba N, Novack D, Woodring J, et al. (2000) Estrogen deficiency induces bone loss by enhancing T-cell production of TNF-α. J Clin Invest 106:1229–37.

    PubMed  CAS  Google Scholar 

  34. Centrella M, McCarthy TL, Canalis E (1988) Tumor necrosis factor-α inhibits collagen synthesis and alkaline phosphatase activity independently of its effect on deoxyribonucleic acid synthesis in osteoblastenriched bone cell cultures. Endocrinology 123:1442–8.

    PubMed  CAS  Google Scholar 

  35. Chabaud M, Miossec P (2001) The combination of tumor necrosis factor α blockade with interleukin-1 and interleukin-17 blockade is more effective for controlling synovial inflammation and bone resorption in an ex vivo model. Arthritis Rheum 44:1293–303.

    Article  PubMed  CAS  Google Scholar 

  36. Chae HJ, Chae SW, Kang JS, Bang BG, Cho SB, Park RK, et al. (2000) Dexamethasone suppresses tumor necrosis factor-α — induced apoptosis in osteoblasts: possible role for ceramide. Endocrinology 141:2904–13.

    Article  PubMed  CAS  Google Scholar 

  37. Chaudhary LR, Spelsberg TC, Riggs BL (1992) Production of various cytokines by normal human osteoblastlike cells in response to interleukin-1 beta and tumor necrosis factor-α: lack of regulation by 17 beta-estradiol. Endocrinology 130:2528–34.

    Article  PubMed  CAS  Google Scholar 

  38. Chen S, Guttridge DC, Tang E, Shi S, Guan K, Wang CY (2001) Suppression of tumor necrosis factor-mediated apoptosis by nuclear factor kappaB-independent bone morphogenetic protein/Smad signaling. J Biol Chem 276:39259–63.

    PubMed  CAS  Google Scholar 

  39. Chua CC, Chua BH, Chen Z, Landy C, Hamdy RC (2002) TGF-beta1 inhibits multiple caspases induced by TNF-α in murine osteoblastic MC3T3-E1 cells. Biochim Biophys Acta 1593:1–8.

    PubMed  CAS  Google Scholar 

  40. Chung KY, Agarwal A, Uitto J, Mauviel A (1996) An AP-1 binding sequence is essential for regulation of the human α2(I) collagen (COL1A2) promoter activity by transforming growth factor-beta. J Biol Chem 271:3272–8.

    PubMed  CAS  Google Scholar 

  41. Darnay BG, Ni J, Moore PA, Aggarwal BB (1999) Activation of Nf-κB by RANK requires tumor necrosis factor receptor-associated factor (TRAF) 6 and Nf-κB-inducing kinase. Identification of a novel TRAF6 interaction motif. J Biol Chem 274:7724–31.

    Article  PubMed  CAS  Google Scholar 

  42. de Bart AC, Quax PH, Lowik CW, Verheijen JH (1995) Regulation of plasminogen activation, matrix metalloproteinases and urokinase-type plasminogen activator-mediated extracellular matrix degradation in human osteosarcoma cell line MG63 by interleukin-1 α. J Bone Miner Res 10:1374–84.

    PubMed  Google Scholar 

  43. De Bosscher K, Vanden Berghe W, Vermeulen L, Plaisance S, Boone E, Haegeman G (2000) Glucocorticoids repress Nf-κB-driven genes by disturbing the interaction of p65 with the basal transcription machinery, irrespective of coactivator levels in the cell. Proc Natl Acad Sci USA 97:3919–24.

    PubMed  Google Scholar 

  44. de Brum-Fernandes AJ, Laporte S, Heroux M, Lora M, Patry C, Menard HA, et al. (1994) Expression of prostaglandin endoperoxide synthase-1 and prostaglandin endoperoxide synthase-2 in human osteoblasts. Biochem Biophys Res Commun 198:955–60.

    PubMed  Google Scholar 

  45. Delaisse JM, Eeckhout Y, Vaes G (1988) Bone-resorbing agents affect the production and distribution of procollagenase as well as the activity of collagenase in bone tissue. Endocrinology 123:264–76.

    Article  PubMed  CAS  Google Scholar 

  46. Ducy P, Zhang R, Geoffroy V, Ridall AL, Karsenty G (1997) Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation Cell 89:747–54.

    Article  PubMed  CAS  Google Scholar 

  47. Eghbali-Fatourechi G, Khosla S, Sanyal A, Boyle WJ, Lacey DL, Riggs BL (2003) Role of RANK ligand in mediating increased bone resorption in early postmenopausal women. J Clin Invest 111:1221–30.

    Article  PubMed  CAS  Google Scholar 

  48. Evans DB, Bunning RA, Russell RG (1990) The effects of recombinant human interleukin-1 beta on cellular proliferation and the production of prostaglandin E2, plasminogen activator, osteocalcin and alkaline phosphatase by osteoblast-like cells derived from human bone. Biochem Biophys Res Commun 166:208–16.

    Article  PubMed  CAS  Google Scholar 

  49. Farley JR, Stilt-Coffing B (2001) Apoptosis may determine the release of skeletal alkaline phosphatase activity from human osteoblast-line cells. Calcif Tissue Int 68:43–52.

    Article  PubMed  CAS  Google Scholar 

  50. Farmer PK, He X, Schmitz ML, Rubin J, Nanes MS (2000) Inhibitory effect of Nf-κB on 1,25-dihydroxyvitamin D(3) and retinoid X receptor function. Am J Physiol Endocrinol Metab 279:E213–20.

    PubMed  CAS  Google Scholar 

  51. Felix R, Cecchini MG, Hofstetter W, Guenther HL, Fleisch H (1991) Production of granulocyte-macrophage (GM-CSF) and granulocyte colonystimulating factor (G-CSF) by rat clonal osteoblastic cell population CRP 10/30 and the immortalized cell line IRC10/30-myc1 stimulated by tumor necrosis factor α. Endocrinology 128:661–7.

    PubMed  CAS  Google Scholar 

  52. Felix R, Fleisch H, Elford PR (1989) Bone-resorbing cytokines enhance release of macrophage colonystimulating activity by the osteoblastic cell MC3T3-E1. Calcif Tissue Int 44:356–60.

    PubMed  CAS  Google Scholar 

  53. Feng X, Teitelbaum SL, Quiroz ME, Cheng SL, Lai CF, Avioli LV, et al. (2000) Sp1/Sp3 and PU.1 differentially regulate beta(5) integrin gene expression in macrophages and osteoblasts. J Biol Chem 275:8331–40.

    PubMed  CAS  Google Scholar 

  54. Fernandez-Martin JL, Kurian S, Farmer P, Nanes MS (1998) Tumor necrosis factor activates a nuclear inhibitor of vitamin D and retinoid-X receptors. Mol Cell Endocrinol 141:65–72.

    Article  PubMed  CAS  Google Scholar 

  55. Fox HS, Bond BL, Parslow TG (1991) Estrogen regulates the IFN-gamma promoter. J Immunol 146:4362–7.

    PubMed  CAS  Google Scholar 

  56. Fox SW, Chambers TJ (2000) Interferon-gamma directly inhibits TRANCE-induced osteoclastogenesis. Biochem Biophys Res Commun 276:868–72.

    Article  PubMed  CAS  Google Scholar 

  57. Franzoso G, Carlson L, Xing L, Poljak L, Shores EW, Brown KD, et al. (1997) Requirement for Nf-κB in osteoclast and B-cell development. Genes Dev 11:3482–96.

    PubMed  CAS  Google Scholar 

  58. Fuller K, Murphy C, Kirstein B, Fox SW, Chambers TJ (2002) TNF α potently activates osteoclasts, through a direct action independent of and strongly synergistic with RANKL. Endocrinology 143:1108–18.

    Article  PubMed  CAS  Google Scholar 

  59. Galibert L, Tometsko ME, Anderson DM, Cosman D, Dougall WC (1998) The involvement of multiple tumor necrosis factor receptor (TNFR)-associated factors in the signaling mechanisms of receptor activator of Nf-κB, a member of the TNFR superfamily. J Biol Chem. 273:34120–7.

    Article  PubMed  CAS  Google Scholar 

  60. Galien R, Garcia T (1997) Estrogen receptor impairs interleukin-6 expression by preventing protein binding on the Nf-κB site. Nucleic Acids Res 25:2424–9.

    Article  PubMed  CAS  Google Scholar 

  61. Gerstenfeld LC, Cho TJ, Kon T, Aizawa T, Cruceta J, Graves BD, et al. (2001) Impaired intramembranous bone formation during bone repair in the absence of tumor necrosis factor-α signaling. Cells Tissues Organs 169:285–94.

    Article  PubMed  CAS  Google Scholar 

  62. Gilbert L, Brantley A, Rubin J, Nanes MS (2002) The p55 TNF receptor mediates TNF inhibition of osteoblast differentiation. J Bone Miner Res 17:SU205.

    Google Scholar 

  63. Gilbert L, He X, Farmer P, Boden S, Kozlowski M, Rubin J, et al. (2000) Inhibition of osteoblast differentiation by tumor necrosis factor-α. Endocrinology 141:3956–64.

    Article  PubMed  CAS  Google Scholar 

  64. Gilbert L, He X, Farmer P, Rubin J, Drissi H, van WAJ, et al. (2002) Expression of the osteoblast differentiation factor RUNX2 (Cbfa1/AML3/Pebp2 αA) is inhibited by tumor necrosis factor-α. J Biol Chem 277:2695–701.

    PubMed  CAS  Google Scholar 

  65. Gilbert LC, He, X., Kauppi, A., Rubin, J., Nanes, M.S. (2003) Inhibition of osteoblast differentiation by TNF-α is associated with suppression of osterix expression. J Bone Mineral Res 18:SU177.

    Google Scholar 

  66. Gimble JM, Hudson J, Henthorn J, Hua XX, Burstein SA (1991) Regulation of interleukin 6 expression in murine bone marrow stromal cells. Exp Hematol 19:1055–60.

    PubMed  CAS  Google Scholar 

  67. Girasole G, Jilka RL, Passeri G, Boswell S, Boder G, Williams DC, et al. (1992) 17 beta-estradiol inhibits interleukin-6 production by bone marrow-derived stromal cells and osteoblasts in vitro: a potential mechanism for the antiosteoporotic effect of estrogens. J Clin Invest 89:883–91.

    PubMed  CAS  Google Scholar 

  68. Gourley T, Roys S, Lukacs NW, Kunkel SL, Flavell RA, Chang CH (1999) A novel role for the major histocompatibility complex class II transactivator CIITA in the repression of IL-4 production. Immunity 10:377–86.

    Article  PubMed  CAS  Google Scholar 

  69. Gowen M, Chapman K, Littlewood A, Hughes D, Evans D, Russell G (1990) Production of tumor necrosis factor by human osteoblasts is modulated by other cytokines, but not by osteotropic hormones. Endocrinology 126:1250–5.

    PubMed  CAS  Google Scholar 

  70. Gowen M, MacDonald BR, Russell RG (1988) Actions of recombinant human gamma-interferon and tumor necrosis factor α on the proliferation and osteoblastic characteristics of human trabecular bone cells in vitro. Arthritis Rheum 31:1500–7.

    PubMed  CAS  Google Scholar 

  71. Hanevold CD, Yamaguchi DT, Jordan SC (1993) Tumor necrosis factor α modulates parathyroid hormone action in UMR-106-01 osteoblastic cells. J Bone Miner Res 8:1191–200.

    PubMed  CAS  Google Scholar 

  72. Harant H, Andrew PJ, Reddy GS, Foglar E, Lindley IJ (1997) 1 α,25-dihydroxyvitamin D3 and a variety of its natural metabolites transcriptionally repress nuclear-factor-kappaB-mediated interleukin-8 gene expression. Eur J Biochem 250:63–71.

    Article  PubMed  CAS  Google Scholar 

  73. Harrison JR, Kleinert LM, Kelly PL, Krebsbach PH, Woody C, Clark S, et al. (1998) Interleukin-1 represses COLIA1 promoter activity in calvarial bones of transgenic ColCAT mice in vitro and in vivo. J Bone Miner Res 13:1076–83.

    PubMed  CAS  Google Scholar 

  74. Harrison JR, Lorenzo JA, Kawaguchi H, Raisz LG, Pilbeam C (1994) Stimulation of prostaglandin E2 production by interleukin-1α and transforming growth factor α in osteoblastic MC3T3-E1 cells. J Bone Miner Res 9:817–23.

    PubMed  CAS  Google Scholar 

  75. Hatamochi A, Mori K, Ueki H (1994) Role of cytokines in controlling connective tissue gene expression. Arch Dermatol Res 287:115–21.

    Article  PubMed  CAS  Google Scholar 

  76. Hernandez I, de la Torre P, Rey-Campos J, Garcia I, Sanchez JA, Munoz R, et al. (2000) Collagen α1(I) gene contains an element responsive to tumor necrosis factor-α located in the 5′ untranslated region of its first exon. DNA Cell Biol 19:341–52.

    PubMed  CAS  Google Scholar 

  77. Hierl T, Borcsok I, Sommer U, Ziegler R, Kasperk C (1998) Regulation of interleukin-6 expression in human osteoblastic cells in vitro. Exp Clin Endocrinol Diabetes 106:324–33.

    Article  PubMed  CAS  Google Scholar 

  78. Hill PA, Tumber A, Meikle MC (1997) Multiple extracellular signals promote osteoblast survival and apoptosis. Endocrinology 138:3849–58.

    PubMed  CAS  Google Scholar 

  79. Hock JM, Krishnan V, Onyia JE, Bidwell JP, Milas J, Stanislaus D (2001) Osteoblast apoptosis and bone turnover. J Bone Miner Res 16:975–84.

    PubMed  CAS  Google Scholar 

  80. Hofbauer LC, Heufelder AE (2001) Role of receptor activator of nuclear factor-kappaB ligand and osteoprotegerin in bone cell biology. J Mol Med 79:243–53.

    Article  PubMed  CAS  Google Scholar 

  81. Hofbauer LC, Lacey DL, Dunstan CR, Spelsberg TC, Riggs BL, Khosla S (1999) Interleukin-1beta and tumor necrosis factor-α, but not interleukin-6, stimulate osteoprotegerin ligand gene expression in human osteoblastic cells. Bone 25:255–9.

    Article  PubMed  CAS  Google Scholar 

  82. Horowitz MC, Xi Y, Wilson K, Kacena MA (2001) Control of osteoclastogenesis and bone resorption by members of the TNF family of receptors and ligands. Cytokine Growth Factor Rev 12:9–18.

    Article  PubMed  CAS  Google Scholar 

  83. Hukkanen M, Hughes FJ, Buttery LD, Gross SS, Evans TJ, Seddon S, et al. (1995) Cytokine-stimulated expression of inducible nitric oxide synthase by mouse, rat, and human osteoblast-like cells and its functional role in osteoblast metabolic activity. Endocrinology 136:5445–53.

    Article  PubMed  CAS  Google Scholar 

  84. Inagaki Y, Truter S, Tanaka S, Di Liberto M, Ramirez F (1995) Overlapping pathways mediate the opposing actions of tumor necrosis factor-α and transforming growth factor-beta on α2(I) collagen gene transcription. J Biol Chem 270:3353–8.

    PubMed  CAS  Google Scholar 

  85. Iraburu MJ, Dominguez-Rosales JA, Fontana L, Auster A, Garcia-Trevijano ER, Covarrubias-Pinedo A, et al. (2000) Tumor necrosis factor α down-regulates expression of the α1(I) collagen gene in rat hepatic stellate cells through a p20C/EBPbeta-and C/EBPdelta-dependent mechanism. Hepatology 31:1086–93.

    Article  PubMed  CAS  Google Scholar 

  86. Isaacs SD, Fan X, Fan D, Gewant H, Murphy TC, Farmer P, et al. (1999) Role of NFkappaB in the regulation of macrophage colony stimulating factor by tumor necrosis factor-α in ST2 bone stromal cells. J Cell Physiol 179:193–200.

    Article  PubMed  CAS  Google Scholar 

  87. Ishimi Y, Miyaura C, Jin CH, Akatsu T, Abe E, Nakamura Y, et al. (1990) IL-6 is produced by osteoblasts and induces bone resorption. J Immunol 145:3297–303.

    PubMed  CAS  Google Scholar 

  88. Janssens S, Beyaert R (2003) Functional diversity and regulation of different interleukin-1 receptor-associated kinase (IRAK) family members. Mol Cell 11:293–302.

    Article  PubMed  CAS  Google Scholar 

  89. Javed A, Barnes GL, Jasanya BO, Stein JL, Gerstenfeld L, Lian JB, et al. (2001) runt homology domain transcription factors (Runx, Cbfa, and AML) mediate repression of the bone sialoprotein promoter: evidence for promoter context-dependent activity of Cbfa proteins. Mol Cell Biol 21:2891–905.

    Article  PubMed  CAS  Google Scholar 

  90. Jefferies C, Bowie A, Brady G, Cooke EL, Li X, O’Neill LA (2001) Transactivation by the p65 subunit of Nf-κB in response to interleukin-1 (IL-1) involves MyD88, IL-1 receptor-associated kinase 1, TRAF-6, and Rac1. Mol Cell Biol 21:4544–52.

    Article  PubMed  CAS  Google Scholar 

  91. Jiang Z, Ninomiya-Tsuji J, Qian Y, Matsumoto K, Li X (2002) Interleukin-1 (IL-1) receptor-associated kinase-dependent IL-1-induced signaling complexes phosphorylate TAK1 and TAB2 at the plasma membrane and activate TAK1 in the cytosol. Mol Cell Biol 22:7158–67.

    Article  PubMed  CAS  Google Scholar 

  92. Jilka RL, Weinstein RS, Bellido T, Parfitt AM, Manolagas SC (1998) Osteoblast programmed cell death (apoptosis): modulation by growth factors and cytokines. J Bone Miner Res 13:793–802.

    PubMed  CAS  Google Scholar 

  93. Jimi E, Ikebe T, Takahashi N, Hirata M, Suda T, Koga T (1996) Interleukin-1α activates all NF-kappa-b-like factor in osteoclast-like cells. Journal of Biological Chemistry 271:4605–4608.

    PubMed  CAS  Google Scholar 

  94. Jimi E, Nakamura I, Ikebe T, Akiyama S, Takahashi N, Suda T (1998) Activation of Nf-κB is involved in the survival of osteoclasts promoted by interleukin-1. J Biol Chem 273:8799–805.

    Article  PubMed  CAS  Google Scholar 

  95. Kahari VM, Chen YQ, Su MW, Ramirez F, Uitto J (1990) Tumor necrosis factor-α and interferon-gamma suppress the activation of human type I collagen gene expression by transforming growth factor-beta 1. Evidence for two distinct mechanisms of inhibition at the transcriptional and posttranscriptional levels. J Clin Invest 86:1489–95.

    PubMed  CAS  Google Scholar 

  96. Kaji K, Katogi R, Azuma Y, Naito A, Inoue JI, Kudo A (2001) Tumor necrosis factor α-induced osteoclastogenesis requires tumor necrosis factor receptor-associated factor 6. J Bone Miner Res 16:1593–9.

    PubMed  CAS  Google Scholar 

  97. Kamada M, Irahara M, Maegawa M, Ohmoto Y, Murata K, Yasui T, et al. (2001) Transient increase in the levels of T-helper 1 cytokines in postmenopausal women and the effects of hormone replacement therapy. Gynecol Obstet Invest 52:82–8.

    Article  PubMed  CAS  Google Scholar 

  98. Kaplan DL, Eielson CM, Horowitz MC, Insogna KL, Weir EC (1996) Tumor necrosis factor-α induces transcription of the colony-stimulating factor-1 gene in murine osteoblasts. J Cell Physiol 168:199–208.

    Article  PubMed  CAS  Google Scholar 

  99. Kassem M, Harris SA, Spelsberg TC, Riggs BL (1996) Estrogen inhibits interleukin-6 production and gene expression in a human osteoblastic cell line with high levels of estrogen receptors. J Bone Miner Res 11:193–9.

    PubMed  CAS  Google Scholar 

  100. Katz MS, Gutierrez GE, Mundy GR, Hymer TK, Caulfield MP, McKee RL (1992) Tumor necrosis factor and interleukin 1 inhibit parathyroid hormone-responsive adenylate cyclase in clonal osteoblast-like cells by down-regulating parathyroid hormone receptors. J Cell Physiol 153:206–13.

    Article  PubMed  CAS  Google Scholar 

  101. Kawaguchi H, Yavari R, Stover ML, Rowe DW, Raisz LG, Pilbeam CC (1994) Measurement of interleukin-1 stimulated constitutive prostaglandin G/H synthase (cyclooxygenase) mRNA levels in osteoblastic MC3T3-E1 cells using competitive reverse transcriptase polymerase chain reaction. Endocr Res 20:219–33.

    PubMed  CAS  Google Scholar 

  102. Kern B, Shen J, Starbuck M, Karsenty G (2001) Cbfa1 contributes to the osteoblast-specific expression of type I collagen genes. J Biol Chem 276:7101–7.

    Article  PubMed  CAS  Google Scholar 

  103. Khosla S, Atkinson EJ, Dunstan CR, O’Fallon WM (2002) Effect of estrogen versus testosterone on circulating osteoprotegerin and other cytokine levels in normal elderly men. J Clin Endocrinol Metab 87:1550–4.

    PubMed  CAS  Google Scholar 

  104. Kim CH, Kang BS, Lee TK, Park WH, Kim JK, Park YG, et al. (2002) IL-1beta regulates cellular proliferation, prostaglandin E2 synthesis, plasminogen activator activity, osteocalcin production, and bone resorptive activity of the mouse calvarial bone cells. Immunopharmacol Immunotoxicol 24:395–407.

    PubMed  CAS  Google Scholar 

  105. Kim YM, Im JY, Han SH, Kang HS, Choi I (2000) IFN-gamma up-regulates IL-18 gene expression via IFN consensus sequence-binding protein and activator protein-1 elements in macrophages. J Immunol 165:3198–205.

    PubMed  CAS  Google Scholar 

  106. Kimble RB, Bain S, Pacifici R (1997) The functional block of TNF but not of IL-6 prevents bone loss in ovariectomized mice. J Bone Miner Res 12:935–41.

    PubMed  CAS  Google Scholar 

  107. Kimble RB, Matayoshi AB, Vannice JL, Kung VT, Williams C, Pacifici R (1995) Simultaneous block of interleukin-1 and tumor necrosis factor is required to completely prevent bone loss in the early postovariectomy period. Endocrinology 136:3054–61.

    Article  PubMed  CAS  Google Scholar 

  108. Kimble RB, Srivastava S, Ross FP, Matayoshi A, Pacifici R (1996) Estrogen deficiency increases the ability of stromal cells to support murine osteoclastogenesis via an interleukin-1and tumor necrosis factor-mediated stimulation of macrophage colony-stimulating factor production. J Biol Chem 271:28890–7.

    PubMed  CAS  Google Scholar 

  109. Kitajima I, Soejima Y, Takasaki I, Beppu H, Tokioka T, Maruyama I (1996) Ceramide-induced nuclear translocation of NF-kappa B is a potential mediator of the apoptotic response to TNF-α in murine clonal osteoblasts. Bone 19:263–70.

    Article  PubMed  CAS  Google Scholar 

  110. Kitazawa R, Kimble RB, Vannice JL, Kung VT, Pacifici R (1994) Interleukin-1 receptor antagonist and tumor necrosis factor binding protein decrease osteoclast formation and bone resorption in ovariectomized mice. J Clin Invest 94:2397–406.

    PubMed  CAS  Google Scholar 

  111. Kobayashi K, Takahashi N, Jimi E, Udagawa N, Takami M, Kotake S, et al. (2000) Tumor necrosis factor α stimulates osteoclast differentiation by a mechanism inde-pendent of the ODF/RANKL-RANK interaction. J Exp Med 191:275–86.

    Article  PubMed  CAS  Google Scholar 

  112. Komine M, Kukita A, Kukita T, Ogata Y, Hotokebuchi T, Kohashi O (2001) Tumor necrosis factor-α cooperates with receptor activator of nuclear factor kappaB ligand in generation of osteoclasts in stromal cell-depleted rat bone marrow cell culture. Bone 28:474–83.

    Article  PubMed  CAS  Google Scholar 

  113. Komori T, Yagi H, Nomura S, Yamaguchi A, Sasaki K, Deguchi K, et al. (1997) Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell 89:755–64.

    Article  PubMed  CAS  Google Scholar 

  114. Kose KN, Xie JF, Carnes DL, Graves DT (1996) Proinflammatory cytokines downregulate platelet derived growth factor-α receptor gene expression in human osteoblastic cells. J Cell Physiol 166:188–97.

    Article  PubMed  CAS  Google Scholar 

  115. Kouba DJ, Chung KY, Nishiyama T, Vindevoghel L, Kon A, Klement JF, et al. (1999) Nuclear factor-kappa B mediates TNF-α inhibitory effect on α2(I) collagen (COL1A2) gene transcription in human dermal fibroblasts. J Immunol 162:4226–34.

    PubMed  CAS  Google Scholar 

  116. Kudo O, Fujikawa Y, Itonaga I, Sabokbar A, Torisu T, Athanasou NA (2002) Proinflammatory cytokine (TNFα /IL-1α) induction of human osteoclast formation. J Pathol 198:220–7.

    Article  PubMed  CAS  Google Scholar 

  117. Kumar S, Votta BJ, Rieman DJ, Badger AM, Gowen M, Lee JC (2001) IL-1-and TNF-induced bone resorption is mediated by p38 mitogen activated protein kinase. J Cell Physiol 187:294–303.

    Article  PubMed  CAS  Google Scholar 

  118. Kuno H, Kurian SM, Hendy GN, White J, deLuca HF, Evans CO, et al. (1994) Inhibition of 1,25-dihydroxyvitamin D3 stimulated osteocalcin gene transcription by tumor necrosis factor-α: structural determinants within the vitamin D response element. Endocrinology 134:2524–31.

    Article  PubMed  CAS  Google Scholar 

  119. Kuroki T, Shingu M, Koshihara Y, Nobunaga M (1994) Effects of cytokines on alkaline phosphatase and osteocalcin production, calcification and calcium release by human osteoblastic cells. Br J Rheumatol 33:224–30.

    PubMed  CAS  Google Scholar 

  120. Kurokouchi K, Kambe F, Yasukawa K, Izumi R, Ishiguro N, Iwata H, et al. (1998) TNF-α increases expression of IL-6 and ICAM-1 genes through activation of Nf-κB in osteoblast-like ROS17/2.8 cells. J Bone Miner Res 13:1290–9.

    PubMed  CAS  Google Scholar 

  121. Kusano K, Miyaura C, Inada M, Tamura T, Ito A, Nagase H, et al. (1998) Regulation of matrix metalloproteinases (MMP-2,-3,-9, and-13) by interleukin-1 and interleukin-6 in mouse calvaria: association of MMP induction with bone resorption. Endocrinology 139:1338–45.

    Article  PubMed  CAS  Google Scholar 

  122. Lacey DL, Grosso LE, Moser SA, Erdmann J, Tan HL, Pacifici R, et al. (1993) IL-1-induced murine osteoblast IL-6 production is mediated by the type 1 IL-1 receptor and is increased by 1,25 dihydroxyvitamin D3. J Clin Invest 91:1731–42.

    PubMed  CAS  Google Scholar 

  123. Lam J, Takeshita S, Barker JE, Kanagawa O, Ross FP, Teitelbaum SL (2000) TNF-α induces osteoclastogenesis by direct stimulation of macrophages exposed to permissive levels of RANK ligand. J Clin Invest 106:1481–8.

    PubMed  CAS  Google Scholar 

  124. Lee SE, Chung WJ, Kwak HB, Chung CH, Kwack KB, Lee ZH, et al. (2001) Tumor necrosis factor-α supports the survival of osteoclasts through the activation of Akt and ERK. J Biol Chem 276:49343–9.

    PubMed  CAS  Google Scholar 

  125. Lee SK, Kalinowski JF, Jastrzebski SL, Puddington L, Lorenzo JA (2003) Interleukin-7 is a direct inhibitor of in vitro osteoclastogenesis. Endocrinology 144:3524–31.

    PubMed  CAS  Google Scholar 

  126. Lee ZH, Lee SE, Kim CW, Lee SH, Kim SW, Kwack K, et al. (2002) IL-1α stimulation of osteoclast survival through the PI 3-kinase/Akt and ERK pathways. J Biochem (Tokyo) 131:161–6.

    PubMed  CAS  Google Scholar 

  127. Li YP, Stashenko P (1992) Proinflammatory cytokines tumor necrosis factor-α and IL-6, but not IL-1, down-regulate the osteocalcin gene promoter. J Immunol 148:788–94.

    PubMed  CAS  Google Scholar 

  128. Liel Y, Shany S, Smirnoff P, Schwartz B (1999) Estrogen increases 1,25-dihydroxyvitamin D receptors expression and bioresponse in the rat duodenal mucosa. Endocrinology 140:280–5.

    Article  PubMed  CAS  Google Scholar 

  129. Lindberg MK, Erlandsson M, Alatalo SL, Windahl S, Andersson G, Halleen JM, et al. (2001) Estrogen receptor alpha, but not estrogen receptor beta, is involved in the regulation of the OPG/RANKL (osteoprotegerin/receptor activator of NF-kappa B ligand) ratio and serum interleukin-6 in male mice. J Endocrinol 171:425–33.

    PubMed  CAS  Google Scholar 

  130. Littlewood AJ, Russell J, Harvey GR, Hughes DE, Russell RG, Gowen M (1991) The modulation of the expression of IL-6 and its receptor in human osteoblasts in vitro. Endocrinology 129:1513–20.

    PubMed  CAS  Google Scholar 

  131. Logan TF, Gooding W, Kirkwood JM, Shadduck RK (1996) Tumor necrosis factor administration is associated with increased endogenous production of M-CSF and G-CSF but not GM-CSF in human cancer patients. Exp Hematol 24:49–53.

    PubMed  CAS  Google Scholar 

  132. Lorenzo JA, Pilbeam CC, Kalinowski JF, Hibbs MS (1992) Production of both 92-and 72-kDa gelatinases by bone cells. Matrix 12:282–90.

    PubMed  CAS  Google Scholar 

  133. Lu X, Fiester, P., Rubin, J., Nanes M.S. (2003) NfkB suppression of VDR transactivaation requires the Rel Homology Domain of p65. J Bone Mineral Res 18:F459.

    Google Scholar 

  134. Luchin A, Suchting S, Merson T, Rosol TJ, Hume DA, Cassady AI, et al. (2001) Genetic and physical interactions between Microphthalmia transcription factor and PU.1 are necessary for osteoclast gene expression and differentiation. J Biol Chem 276:36703–10.

    Article  PubMed  CAS  Google Scholar 

  135. Manji SS, Zhou H, Findlay DM, Martin TJ, Ng KW (1995) Tumor necrosis factor-α facilitates nuclear actions of retinoic acid to regulate expression of the alkaline phosphatase gene in preosteoblasts. J Biol Chem 270:8958–62.

    PubMed  CAS  Google Scholar 

  136. Mann GN, Jacobs TW, Buchinsky FJ, Armstrong EC, Li M, Ke HZ, et al. (1994) Interferon-gamma causes loss of bone volume in vivo and fails to ameliorate cyclosporin A-induced osteopenia. Endocrinology 135:1077–1083.

    Article  PubMed  CAS  Google Scholar 

  137. Mann J, Oakley F, Johnson PW, Mann DA (2002) CD40 induces interleukin-6 gene transcription in dendritic cells: regulation by TRAF2, AP-1, NF-kappa B, AND CBF1. J Biol Chem 277:17125–38.

    PubMed  CAS  Google Scholar 

  138. Manolagas SC (1995) Role of cytokines in bone resorption. Bone 17:63S–67S.

    Article  PubMed  CAS  Google Scholar 

  139. Marusic A, Kalinowski JF, Harrison JR, Centrella M, Raisz LG, Lorenzo JA (1991) Effects of transforming growth factor-beta and IL-1α on prostaglandin synthesis in serum-deprived osteoblastic cells. J Immunol 146:2633–8.

    PubMed  CAS  Google Scholar 

  140. Mayur N, Lewis S, Catherwood BD, Nanes MS (1993) Tumor necrosis factor-α decreases 1,25-dihydroxyvitamin D3 receptors in osteoblastic ROS 17/2.8 cells. J Bone Miner Res 8:997–1003.

    PubMed  CAS  Google Scholar 

  141. McCarthy TL, Ji C, Chen Y, Kim KK, Imagawa M, Ito Y, et al. (2000) Runt domain factor (Runx)-dependent effects on CCAAT/ enhancer-binding protein delta expression and activity in osteoblasts. J Biol Chem 275:21746–53.

    Article  PubMed  CAS  Google Scholar 

  142. McSheehy PM, Chambers TJ (1986) Osteoblastic cells mediate osteoclastic responsiveness to parathyroid hormone. Endocrinology 118:824–8.

    PubMed  CAS  Google Scholar 

  143. McSheehy PM, Chambers TJ (1986) Osteoblast-like cells in the presence of parathyroid hormone release soluble factor that stimulates osteoclastic bone resorption. Endocrinology 119:1654–9.

    PubMed  CAS  Google Scholar 

  144. McSheehy PM, Chambers TJ (1987) 1,25-Dihydroxyvitamin D3 stimulates rat osteoblastic cells to release a soluble factor that increases osteoclastic bone resorption. J Clin Invest 80:425–9.

    PubMed  CAS  Google Scholar 

  145. Meikle MC, Bord S, Hembry RM, Reynolds JJ (1995) The synthesis of collagenase, gelatinase-A (72kDa) and-B (95 kDa), and TIMP-1 and-2 by human osteoblasts from normal and arthritic bone. Bone 17:255–60.

    Article  PubMed  CAS  Google Scholar 

  146. Min YK, Rao Y, Okada Y, Raisz LG, Pilbeam CC (1998) Regulation of prostaglandin G/H synthase-2 expression by interleukin-1 in human osteoblast-like cells. J Bone Miner Res 13:1066–75.

    PubMed  CAS  Google Scholar 

  147. Mori K, Hatamochi A, Ueki H, Olsen A, Jimenez SA (1996) The transcription of human α1(I) procollagen gene (COL1A1) is suppressed by tumour necrosis factor-α through proximal short promoter elements: evidence for suppression mechanisms mediated by two nuclear-factorbinding sites. Biochem J 319(Pt 3):811–6.

    PubMed  CAS  Google Scholar 

  148. Muegge K, Durum S (1990) Cytokines and Transcription Factors. [Review]. Cytokine 2:1–8.

    Article  PubMed  CAS  Google Scholar 

  149. Muhlethaler-Mottet A, Di Berardino W, Otten LA, Mach B (1998) Activation of the MHC class II transactivator CIITA by interferon-gamma requires cooperative interaction between Stat1 and USF-1. Immunity 8:157–66.

    Article  PubMed  CAS  Google Scholar 

  150. Muhlethaler-Mottet A, Otten LA, Steimle V, Mach B (1997) Expression of MHC class II molecules in different cellular and functional compartments is controlled by differential usage of multiple promoters of the transactivator CIITA. Embo J 16:2851–60.

    Article  PubMed  CAS  Google Scholar 

  151. Murphy KM, Ouyang W, Farrar JD, Yang J, Ranganath S, Asnagli H, et al. (2000) Signaling and transcription in T helper development. Annu Rev Immunol 18:451–94.

    Article  PubMed  CAS  Google Scholar 

  152. Nagarajan UM, Bushey A, Boss JM (2002) Modulation of gene expression by the MHC class II transactivator. J Immunol 169:5078–88.

    PubMed  Google Scholar 

  153. Nagarajan UM, Lochamy J, Chen X, Beresford GW, Nilsen R, Jensen PE, et al. (2002) Class II transactivator is required for maximal expression of HLA-DOB in B cells. J Immunol 168:1780–6.

    PubMed  CAS  Google Scholar 

  154. Nagy Z, Radeff J, Stern PH (2001) Stimulation of interleukin-6 promoter by parathyroid hormone, tumor necrosis factor-α, and interleukin-1beta in UMR-106 osteoblastic cells is inhibited by protein kinase C antagonists. J Bone Miner Res 16:1220–7.

    PubMed  CAS  Google Scholar 

  155. Nakase T, Takaoka K, Masuhara K, Shimizu K, Yoshikawa H, Ochi T (1997) Interleukin-1 beta enhances and tumor necrosis factor-α inhibits bone morphogenetic protein-2-induced alkaline phosphatase activity in MC3T3-E1 osteoblastic cells. Bone 21:17–21.

    Article  PubMed  CAS  Google Scholar 

  156. Nakashima K, Zhou X, Kunkel G, Zhang Z, Deng JM, Behringer RR, et al. (2002) The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell 108:17–29.

    Article  PubMed  CAS  Google Scholar 

  157. Nanes MS, Kuno H, Demay MB, Kurian M, Hendy GN, DeLuca HF, et al. (1994) A single up-stream element confers responsiveness to 1,25-dihydroxyvitamin D3 and tumor necrosis factor-α in the rat osteocalcin gene. Endocrinology 134:1113–20.

    Article  PubMed  CAS  Google Scholar 

  158. Nanes MS, McKoy WM, Marx SJ (1989) Inhibitory effects of tumor necrosis factor-α and interferongamma on deoxyribonucleic acid and collagen synthesis by rat osteosarcoma cells (ROS 17/2.8). Endocrinology 124:339–45.

    PubMed  CAS  Google Scholar 

  159. Nanes MS, Rubin J, Titus L, Hendy GN, Catherwood B (1991) Tumor necrosis factor-α inhibits 1,25-dihydroxyvitamin D3-stimulated bone Gla protein synthesis in rat osteosarcoma cells (ROS 17/2.8) by a pretranslational mechanism. Endocrinology 128:2577–82.

    PubMed  CAS  Google Scholar 

  160. Need AG, Morris HA, Horowitz M, Scopacasa E, Nordin BE (1998) Intestinal calcium absorption in men with spinal osteoporosis. Clin Endocrinol (Oxf) 48:163–8.

    CAS  Google Scholar 

  161. Nissen RM, Yamamoto KR (2000) The glucocorticoid receptor inhibits NFkappaB by interfering with serine-2 phosphorylation of the RNA polymerase II carboxyterminal domain. Genes Dev 14:2314–29.

    Article  PubMed  CAS  Google Scholar 

  162. Nomura S, Sakuma T, Higashibata Y, Oboki K, Sato M (2001) Molecular cause of the severe functional deficiency in osteoclasts by an arginine deletion in the basic domain of Mi transcription factor. J Bone Miner Metab 19:183–7.

    Article  PubMed  CAS  Google Scholar 

  163. Okada Y, Morimoto I, Ura K, Watanabe K, Eto S, Kumegawa M, et al. (2002) Cell-to-Cell adhesion via intercellular adhesion molecule-1 and leukocyte function-associated antigen-1 pathway is involved in 1α,25(OH)2D3, PTH and IL-1α-induced osteoclast differentiation and bone resorption. Endocr J 49:483–95.

    Article  PubMed  CAS  Google Scholar 

  164. Okahashi N, Koide M, Jimi E, Suda T, Nishihara T (1998) Caspases (interleukin-1beta-converting enzyme family proteases) are involved in the regulation of the survival of osteoclasts. Bone 23:33–41.

    Article  PubMed  CAS  Google Scholar 

  165. O’Keefe GM, Nguyen VT, Ping Tang LL, Benveniste EN (2001) IFN-gamma regulation of class II transactivator promoter IV in macrophages and microglia: involvement of the suppressors of cytokine signaling-1 protein. J Immunol 166:2260–9.

    PubMed  CAS  Google Scholar 

  166. Pacifici R (1996) Estrogen, cytokines, and pathogenesis of postmenopausal osteoporosis. J Bone Miner Res 11:1043–51.

    Article  PubMed  CAS  Google Scholar 

  167. Pacifici R, Brown C, Puscheck E, Friedrich E, Slatopolsky E, Maggio D, et al. (1991) Effect of surgical menopause and estrogen replacement on cytokine release from human blood mononuclear cells. Proc Natl Acad Sci USA 88:5134–8.

    PubMed  CAS  Google Scholar 

  168. Pai RK, Askew D, Boom WH, Harding CV (2002) Regulation of class II MHC expression in APCs: roles of types I, III, and IV class II transactivator. J Immunol 169:1326–33.

    PubMed  CAS  Google Scholar 

  169. Panagakos FS, Kumar S (1994) Modulation of proteases and their inhibitors in immortal human osteoblast-like cells by tumor necrosis factor-α in vitro. Inflammation 18:243–65.

    PubMed  CAS  Google Scholar 

  170. Panagakos FS, Kumar S (1995) Differentiation of human osteoblastic cells in culture: modulation of proteases by extracellular matrix and tumor necrosis factor-α. Inflammation 19:423–43.

    Article  PubMed  CAS  Google Scholar 

  171. Pascher E, Perniok A, Becker A, Feldkamp J (1999) Effect of 1α,25(OH)2-vitamin D3 on TNF-α-mediated apoptosis of human primary osteoblast-like cells in vitro. Horm Metab Res 31:653–6.

    Article  PubMed  CAS  Google Scholar 

  172. Passeri G, Girasole G, Manolagas SC, Jilka RL (1994) Endogenous production of tumor necrosis factor by primary cultures of murine calvarial cells: influence on IL-6 production and osteoclast development. Bone Miner 24:109–26.

    PubMed  CAS  Google Scholar 

  173. Pavalko FM, Gerard RL, Ponik SM, Gallagher PJ, Jin Y, Norvell SM (2003) Fluid shear stress inhibits TNF-α-induced apoptosis in osteoblasts: a role for fluid shear stress-induced activation of PI3-kinase and inhibition of caspase-3. J Cell Physiol 194:194–205.

    Article  PubMed  CAS  Google Scholar 

  174. Pruzanski W, Stefanski E, Vadas P, Kennedy BP, van den Bosch H (1998) Regulation of the cellular expression of secretory and cytosolic phospholipases A2, and cyclooxygenase-2 by peptide growth factors. Biochim Biophys Acta 1403:47–56.

    PubMed  CAS  Google Scholar 

  175. Qian Y, Commane M, Ninomiya-Tsuji J, Matsumoto K, Li X (2001) IRAK-mediated translocation of TRAF6 and TAB2 in the interleukin-1-induced activation of NFkappa B. J Biol Chem 276:41661–7.

    PubMed  CAS  Google Scholar 

  176. Ralston SH (1994) Analysis of gene expression in human bone biopsies by polymerase chain reaction: evidence for enhanced cytokine expression in postmenopausal osteoporosis. J Bone Miner Res 9:883–90.

    PubMed  CAS  Google Scholar 

  177. Ralston SH, Russell RG, Gowen M (1990) Estrogen inhibits release of tumor necrosis factor from peripheral blood mononuclear cells in postmenopausal women. J Bone Miner Res 5:983–8.

    PubMed  CAS  Google Scholar 

  178. Ramalho AC, Jullienne A, Couttet P, Graulet AM, Morieux C, de Vernejoul MC, et al. (2001) Effect of oestradiol on cytokine production in immortalized human marrow stromal cell lines. Cytokine 16:126–30.

    Article  PubMed  CAS  Google Scholar 

  179. Rao VH, Singh RK, Delimont DC, Finnell RH, Bridge JA, Neff JR, et al. (1999) Transcriptional regulation of MMP-9 expression in stromal cells of human giant cell tumor of bone by tumor necrosis factor-α. Int J Oncol 14:291–300.

    PubMed  CAS  Google Scholar 

  180. Rickard D, Russell G, Gowen M (1992) Oestradiol inhibits the release of tumour necrosis factor but not interleukin 6 from adult human osteoblasts in vitro. Osteoporos Int 2:94–102.

    Article  PubMed  CAS  Google Scholar 

  181. Rifas L, Halstead LR, Peck WA, Avioli LV, Welgus HG (1989) Human osteoblasts in vitro secrete tissue inhibitor of metalloproteinases and gelatinase but not interstitial collagenase as major cellular products. J Clin Invest 84:686–94.

    PubMed  CAS  Google Scholar 

  182. Rifas L, Kenney JS, Marcelli M, Pacifici R, Cheng SL, Dawson LL, et al. (1995) Production of interleukin-6 in human osteoblasts and human bone marrow stromal cells: evidence that induction by interleukin-1 and tumor necrosis factor-α is not regulated by ovarian steroids. Endocrinology 136:4056–67.

    Article  PubMed  CAS  Google Scholar 

  183. Roggia C, Gao Y, Cenci S, Weitzmann MN, Toraldo G, Isaia G, et al. (2001) Up-regulation of TNF-producing T cells in the bone marrow: a key mechanism by which estrogen deficiency induces bone loss in vivo. Proc Natl Acad Sci USA 98:13960–5.

    Article  PubMed  CAS  Google Scholar 

  184. Romas E, Udagawa N, Zhou H, Tamura T, Saito M, Taga T, et al. (1996) The role of gp130-mediated signals in osteoclast development: regulation of interleukin 11 production by osteoblasts and distribution of its receptor in bone marrow cultures. J Exp Med 183:2581–91.

    Article  PubMed  CAS  Google Scholar 

  185. Rubin J, Fan D, Wade A, Murphy TC, Gewant H, Nanes MS, et al. (2000) Transcriptional regulation of the expression of macrophage colony stimulating factor. Mol Cell Endocrinol 160:193–202.

    Article  PubMed  CAS  Google Scholar 

  186. Salamone LM, Whiteside T, Friberg D, Epstein RS, Kuller LH, Cauley JA (1998) Cytokine production and bone mineral density at the lumbar spine and femoral neck in premenopausal women. Calcif Tissue Int 63:466–70.

    Article  PubMed  CAS  Google Scholar 

  187. Salem ML, Hossain MS, Nomoto K (2000) Mediation of the immunomodulatory effect of beta-estradiol on inflammatory responses by inhibition of recruitment and activation of inflammatory cells and their gene expression of TNF-α and IFN-gamma. Int Arch Allergy Immunol 121:235–45.

    PubMed  CAS  Google Scholar 

  188. Sato K, Satoh T, Shizume K, Yamakawa Y, Ono Y, Demura H, et al. (1992) Prolonged decrease of serum calcium concentration by murine gamma-interferon in hypercalcemic, human tumor (EC-GI)-bearing nude mice. Cancer Res 52:444–9.

    PubMed  CAS  Google Scholar 

  189. Sato M, Morii E, Komori T, Kawahata H, Sugimoto M, Terai K, et al. (1998) Transcriptional regulation of osteopontin gene in vivo by PEBP2αA/CBFA1 and ETS1 in the skeletal tissues. Oncogene 17:1517–25.

    PubMed  CAS  Google Scholar 

  190. Scharla SH, Strong DD, Mohan S, Chevalley T, Linkhart TA (1994) Effect of tumor necrosis factor-α on the expression of insulin-like growth factor I and insulinlike growth factor binding protein 4 in mouse osteoblasts. Eur J Endocrinol 131:293–301.

    Article  PubMed  CAS  Google Scholar 

  191. Scheinman RI, Gualberto A, Jewell CM, Cidlowski JA, Baldwin AS, Jr. (1995) Characterization of mechanisms involved in transrepression of NF-kappa B by activated glucocorticoid receptors. Mol Cell Biol 15:943–53.

    PubMed  CAS  Google Scholar 

  192. Schneider HG, Allan EH, Moseley JM, Martin TJ, Findlay DM (1991) Specific down-regulation of parathyroid hormone (PTH) receptors and responses to PTH by tumour necrosis factor-α and retinoic acid in UMR 106-06 osteoblast-like osteosarcoma cells. Biochem J 280(Pt 2):451–7.

    PubMed  CAS  Google Scholar 

  193. Shen V, Kohler G, Jeffrey JJ, Peck WA (1988) Boneresorbing agents promote and interferon-gamma inhibits bone cell collagenase production. J Bone Miner Res 3:657–66.

    Article  PubMed  CAS  Google Scholar 

  194. Shevde NK, Bendixen AC, Dienger KM, Pike JW (2000) Estrogens suppress RANK ligand-induced osteoclast differentiation via a stromal cell independent mechanism involving c-Jun repression. Proc Natl Acad Sci USA 97:7829–34.

    Article  PubMed  CAS  Google Scholar 

  195. Smith DD, Gowen M, Mundy GR (1987) Effects of interferon-gamma and other cytokines on collagen synthesis in fetal rat bone cultures. Endocrinology 120:2494–9.

    PubMed  CAS  Google Scholar 

  196. Srivastava S, Toraldo G, Weitzmann MN, Cenci S, Ross FP, Pacifici R (2001) Estrogen decreases osteoclast formation by down-regulating receptor activator of NF-kappa B ligand (RANKL)-induced JNK activation. J Biol Chem 276:8836–40.

    PubMed  CAS  Google Scholar 

  197. Srivastava S, Weitzmann MN, Cenci S, Ross FP, Adler S, Pacifici R (1999) Estrogen decreases TNF gene expression by blocking JNK activity and the resulting production of c-Jun and JunD. J Clin Invest 104:503–13.

    Article  PubMed  CAS  Google Scholar 

  198. Stashenko P, Obernesser MS, Dewhirst FE (1989) Effect of immune cytokines on bone. Immunol Invest 18:239–49.

    PubMed  CAS  Google Scholar 

  199. Suda T, Kobayashi K, Jimi E, Udagawa N, Takahashi N (2001) The molecular basis of osteoclast differentiation and activation. Novartis Found Symp 232:235–47; discussion 247–50.

    PubMed  CAS  Google Scholar 

  200. Taichman RS, Hauschka PV (1992) Effects of interleukin-1 beta and tumor necrosis factor-α on osteoblastic expression of osteocalcin and mineralized extracellular matrix in vitro. Inflammation 16:587–601.

    Article  PubMed  CAS  Google Scholar 

  201. Takaesu G, Ninomiya-Tsuji J, Kishida S, Li X, Stark GR, Matsumoto K (2001) Interleukin-1 (IL-1) receptor-associated kinase leads to activation of TAK1 by inducing TAB2 translocation in the IL-1 signaling pathway. Mol Cell Biol 21:2475–84.

    Article  PubMed  CAS  Google Scholar 

  202. Takaoka Y, Niwa S, Nagai H (1999) Interleukin-1beta induces interleukin-6 production through the production of prostaglandin E(2) in human osteoblasts, MG-63 cells. J Biochem (Tokyo) 126:553–8.

    PubMed  CAS  Google Scholar 

  203. Takayanagi H, Ogasawara K, Hida S, Chiba T, Murata S, Sato K, et al. (2000) T-cell-mediated regulation of osteoclastogenesis by signalling cross-talk between RANKL and IFN-gamma. Nature 408:600–5.

    PubMed  CAS  Google Scholar 

  204. Tatakis DN, Schneeberger G, Dziak R (1988) Recombinant interleukin-1 stimulates prostaglandin E2 production by osteoblastic cells: synergy with parathyroid hormone. Calcif Tissue Int 42:358–62.

    PubMed  CAS  Google Scholar 

  205. Tatakis DN, Schneeberger G, Dziak R (1991) Recombinant interleukin-1 (IL-1) stimulates prostaglandin E2 production by osteoblastic cells: role of calcium, calmodulin, and cAMP. Lymphokine Cytokine Res 10:95–9.

    PubMed  CAS  Google Scholar 

  206. Thomas JA, Allen JL, Tsen M, Dubnicoff T, Danao J, Liao XC, et al. (1999) Impaired cytokine signaling in mice lacking the IL-1 receptor-associated kinase. J Immunol 163:978–84.

    PubMed  CAS  Google Scholar 

  207. Thomson BM, Mundy GR, Chambers TJ (1987) Tumor necrosis factors-α and β induce osteoblastic cells to stimulate osteoclastic bone resorption. J Immunol 138:775–9.

    PubMed  CAS  Google Scholar 

  208. Thomson BM, Saklatvala J, Chambers TJ (1986) Osteoblasts mediate interleukin 1 stimulation of bone resorption by rat osteoclasts. J Exp Med. 164:104–12.

    Article  PubMed  CAS  Google Scholar 

  209. Tohkin M, Kakudo S, Kasai H, Arita H (1994) Comparative study of inhibitory effects by murine interferon gamma and a new bisphosphonate (alendronate) in hypercalcemic, nude mice bearing human tumor (LJC-1-JCK). Cancer Immunol Immunother 39:155–60.

    PubMed  CAS  Google Scholar 

  210. Tondravi MM, McKercher SR, Anderson K, Erdmann JM, Quiroz M, Maki R, et al. (1997) Osteopetrosis in mice lacking haematopoietic transcription factor PU.1. Nature 386:81–4.

    Article  PubMed  CAS  Google Scholar 

  211. 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-α from T cells. Proc Natl Acad Sci USA 100:125–130.

    Article  PubMed  CAS  Google Scholar 

  212. Tsuboi M, Kawakami A, Nakashima T, Matsuoka N, Urayama S, Kawabe Y, et al. (1999) Tumor necrosis factor-α and interleukin-1beta increase the Fasmediated apoptosis of human osteoblasts. J Lab Clin Med 134:222–31.

    Article  PubMed  CAS  Google Scholar 

  213. Tsutsumimoto T, Kawasaki S, Ebara S, Takaoka K (1999) TNF-α and IL-1beta suppress N-cadherin expression in MC3T3-E1 cells. J Bone Miner Res 14:1751–60.

    PubMed  CAS  Google Scholar 

  214. Tuyt LM, Dokter WH, Birkenkamp K, Koopmans SB, Lummen C, Kruijer W, et al. (1999) Extracellular-regulated kinase 1/2, Jun N-terminal kinase, and c-Jun are involved in NF-kappa B-dependent IL-6 expression in human monocytes. J Immunol 162:4893–902.

    PubMed  CAS  Google Scholar 

  215. Uchida M, Shima M, Shimoaka T, Fujieda A, Obara K, Suzuki H, et al. (2000) Regulation of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) by bone resorptive factors in osteoblastic cells. J Cell Physiol 185:207–14.

    Article  PubMed  CAS  Google Scholar 

  216. Uy HL, Mundy GR, Boyce BF, Story BM, Dunstan CR, Yin JJ, et al. (1997) Tumor necrosis factor enhances parathyroid hormone-related protein-induced hypercalcemia and bone resorption without inhibiting bone formation in vivo. Cancer Res 57:3194–9.

    PubMed  CAS  Google Scholar 

  217. van der Saag PT, Caldenhoven E, van de Stolpe A (1996) Molecular mechanisms of steroid action: a novel type of cross-talk between glucocorticoids and NF-kappa B transcription factors. Eur Respir J Suppl 22:146s–153s.

    Google Scholar 

  218. Vargas SJ, Naprta A, Glaccum M, Lee SK, Kalinowski J, Lorenzo JA (1996) Interleukin-6 expression and histomorphometry of bones from mice deficient in receptors for interleukin-1 or tumor necrosis factor. J Bone Miner Res 11:1736–44.

    PubMed  CAS  Google Scholar 

  219. Vargas SJ, Naprta A, Lee SK, Kalinowski J, Kawaguchi H, Pilbeam CC, et al. (1996) Lack of evidence for an increase in interleukin-6 expression in adult murine bone, bone marrow, and marrow stromal cell cultures after ovariectomy. J Bone Miner Res 11:1926–34.

    PubMed  CAS  Google Scholar 

  220. Verthelyi D, Klinman DM (2000) Sex hormone levels correlate with the activity of cytokine-secreting cells in vivo. Immunology 100:384–90.

    Article  PubMed  CAS  Google Scholar 

  221. Vidal ON, Sjogren K, Eriksson BI, Ljunggren O, Ohlsson C (1998) Osteoprotegerin mRNA is increased by interleukin-1α in the human osteosarcoma cell line MG-63 and in human osteoblast-like cells. Biochem Biophys Res Commun 248:696–700.

    Article  PubMed  CAS  Google Scholar 

  222. Vig E, Green M, Liu Y, Donner DB, Mukaida N, Goebl MG, et al. (1999) Modulation of tumor necrosis factor and interleukin-1-dependent Nf-κB activity by mPLK/IRAK. J Biol Chem 274:13077–84.

    Article  PubMed  CAS  Google Scholar 

  223. Wadleigh DJ, Herschman HR (1999) Transcriptional regulation of the cyclooxygenase-2 gene by diverse ligands in murine osteoblasts. Biochem Biophys Res Commun 264:865–70.

    Article  PubMed  CAS  Google Scholar 

  224. Wagner EF (2002) Functions of AP1 (Fos/Jun) in bone development. Ann Rheum Dis 61Suppl 2:1140–2.

    Google Scholar 

  225. Waldburger JM, Suter T, Fontana A, Acha-Orbea H, Reith W (2001) Selective abrogation of major histocompatibility complex class II expression on extrahematopoietic cells in mice lacking promoter IV of the class II transactivator gene. J Exp Med 194:393–406.

    Article  PubMed  CAS  Google Scholar 

  226. Weitzmann MN, Cenci S, Rifas L, Brown C, Pacifici R (2000) Interleukin-7 stimulates osteoclast formation by up-regulating the T-cell production of soluble osteoclastogenic cytokines. Blood 96:1873–8.

    PubMed  CAS  Google Scholar 

  227. Weitzmann MN, Roggia C, Toraldo G, Weitzmann L, Pacifici R (2002) Increased production of IL-7 uncouples bone formation from bone resorption during estrogen deficiency. J Clin Invest 110:1643–50.

    Article  PubMed  CAS  Google Scholar 

  228. Wiktor-Jedrzejczak W, Urbanowska E, Aukerman SL, Pollard JW, Stanley ER, Ralph P, et al. (1991) Correction by CSF-1 of defects in the osteopetrotic op/op mouse suggests local, developmental, and humoral requirements for this growth factor. Exp Hematol 19:1049–54.

    PubMed  CAS  Google Scholar 

  229. Wood RJ, Fleet JC, Cashman K, Bruns ME, Deluca HF (1998) Intestinal calcium absorption in the aged rat: evidence of intestinal resistance to 1,25(OH)2 vitamin D. Endocrinology 139:3843–8.

    Article  PubMed  CAS  Google Scholar 

  230. Xie JF, Stroumza J, Graves DT (1994) IL-1 down-regulates platelet-derived growth factor-α receptor gene expression at the transcriptional level in human osteoblastic cells. J Immunol 153:378–83.

    PubMed  CAS  Google Scholar 

  231. Xing L, Bushnell TP, Carlson L, Tai Z, Tondravi M, Siebenlist U, et al. (2002) Nf-κB p50 and p52 expression is not required for RANK-expressing osteoclast progenitor formation but is essential for RANK-and cytokine-mediated osteoclastogenesis. J Bone Miner Res 17:1200–10.

    PubMed  CAS  Google Scholar 

  232. Xing L, Carlson L, Story B, Tai Z, Keng P, Siebenlist U, et al. (2003) Expression of either Nf-κB p50 or p52 in osteoclast precursors is required for IL-1-induced bone resorption. J Bone Miner Res 18:260–9.

    PubMed  CAS  Google Scholar 

  233. Xu J, Cissel DS, Varghese S, Whipkey DL, Blaha JD, Graeber GM, et al. (1997) Cytokine regulation of adult human osteoblast-like cell prostaglandin biosynthesis. J Cell Biochem 64:618–31.

    Article  PubMed  CAS  Google Scholar 

  234. Yagi K, Tsuji K, Nifuji A, Shinomiya K, Nakashima K, DeCrombrugghe B, et al. (2003) Bone morphogenetic protein-2 enhances osterix gene expression in chondrocytes. J Cell Biochem 88:1077–83.

    Article  PubMed  CAS  Google Scholar 

  235. Yamin TT, Miller DK (1997) The interleukin-1 receptor-associated kinase is degraded by proteasomes following its phosphorylation. J Biol Chem 272:21540–7.

    Article  PubMed  CAS  Google Scholar 

  236. Yang C PC, Phillips LS, Rubin J, Nanes MS (1998) Paradoxical enhancement of PTH-stimulated IGF-1 gene transcription by TNF-α despite inhibition of IGF-1 mRNA. Bone 23:F041.

    Article  Google Scholar 

  237. Yao GQ, Sun BH, Insogna KL, Weir EC (2000) Nuclear factor-kappaB p50 is required for tumor necrosis factor-α-induced colony-stimulating factor-1 gene expression in osteoblasts. Endocrinology 141:2914–22.

    Article  PubMed  CAS  Google Scholar 

  238. Ye H, Arron JR, Lamothe B, Cirilli M, Kobayashi T, Shevde NK, et al. (2002) Distinct molecular mechanism for initiating TRAF6 signalling. Nature 418:443–7.

    Article  PubMed  CAS  Google Scholar 

  239. Yoshida H, Hayashi S, Kunisada T, Ogawa M, Nishikawa S, Okamura H, et al. (1990) The murine mutation osteopetrosis is in the coding region of the macrophage colony stimulating factor gene. Nature 345:442–4.

    Article  PubMed  CAS  Google Scholar 

  240. Yoshihara R, Shiozawa S, Imai Y, Fujita T (1990) Tumor necrosis factor-α and interferon gamma inhibit proliferation and alkaline phosphatase activity of human osteoblastic SaOS-2 cell line. Lymphokine Res 9:59–66.

    PubMed  CAS  Google Scholar 

  241. Zhang YH, Heulsmann A, Tondravi MM, Mukherjee A, Abu-Amer Y (2001) Tumor necrosis factor-α (TNF) stimulates RANKL-induced osteoclastogenesis via coupling of TNF type 1 receptor and RANK signaling pathways. J Biol Chem 276:563–8.

    PubMed  CAS  Google Scholar 

  242. Zheng SX, Vrindts Y, Lopez M, De Groote D, Zangerle PF, Collette J, et al. (1997) Increase in cytokine production (IL-1 beta, IL-6, TNF-α but not IFN-gamma, GM-CSF or LIF) by stimulated whole blood cells in postmenopausal osteoporosis. Maturitas 26:63–71.

    Article  PubMed  CAS  Google Scholar 

  243. Zou W, Hakim I, Tschoep K, Endres S, Bar-Shavit Z (2001) Tumor necrosis factor-α mediates RANK ligand stimulation of osteoclast differentiation by an autocrine mechanism. J Cell Biochem 83:70–83.

    Article  PubMed  CAS  Google Scholar 

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Authors
  1. Mark S. Nanes
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  2. Roberto Pacifici
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Editors and Affiliations

  1. Department of BioStructure and Function, University of Connecticut Health Center, Farmington, CT, USA

    Felix Bronner PhD

  2. Department of Pharmacology, University of Connecticut Health Center, Farmington, CT, USA

    Felix Bronner PhD

  3. Department of Biology, University of Delaware, Newark, DE, USA

    Mary C Farach-Carson PhD

  4. Division of Endocrinology and Metabolism, Emory University School of Medicine, Veterans Affairs Medical Center, Decatur, GA, USA

    Janet Rubin MD

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Nanes, M.S., Pacifici, R. (2005). Inflammatory Cytokines. In: Bronner, F., Farach-Carson, M.C., Rubin, J. (eds) Bone Resorption. Topics in Bone Biology, vol 2. Springer, London. https://doi.org/10.1007/1-84628-016-8_5

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  • DOI: https://doi.org/10.1007/1-84628-016-8_5

  • Publisher Name: Springer, London

  • Print ISBN: 978-1-85233-812-1

  • Online ISBN: 978-1-84628-016-0

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