• 1
    Rodan GA, Martin TJ. Role of osteoblasts in hormonal control of bone resorption: a hypothesis. Calcif Tissue Int 1981; 33: 34951.
  • 2
    Jimi E, Nakamura I, Amano H, Taguchi Y, Tsurukai T, Tamura M, et al. Osteoclast function is activated by osteoblastic cells through a mechanism involving cell-to-cell contact. Endocrinology 1996; 137: 218790.
  • 3
    Keyszer GM, Heer AH, Gay S. Cytokines and oncogenes in cellular interactions of rheumatoid arthritis. Stem Cells 1994; 12: 7586.
  • 4
    Lerner UH. Regulation of bone metabolism by the kallikrein-kinin system, the coagulation cascade, and the acute-phase reactants. Oral Surg Oral Med Oral Pathol 1994; 78: 48193.
  • 5
    Taubman MA, Kawai T. Involvement of T-lymphocytes in peridontal disease and in direct and indirect induction of bone resorption. Crit Rev Oral Biol Med 2001; 12: 12535.
  • 6
    Aubin JE, Bonnelye E. Osteoprotegerin and its ligand: a new paradigm for regulation of osteoclastogenesis and bone resorption. Osteoporos Int 2000; 11: 90513.
  • 7
    Hofbauer LC, Khosla S, Dunstan CR, Lacey DL, Boyle WJ, Riggs BL. The roles of osteoprotegerin and osteoprotegerin ligand in the paracrine regulation of bone resorption. J Bone Miner Res 2000; 15: 212.
  • 8
    Gravallese EM, Galson DL, Goldring SR, Auron PE. The role of TNF-receptor family members and other TRAF-dependent receptors in bone resorption. Arthritis Res 2001; 3: 612.
  • 9
    Hofbauer LC, Heufelder AE. Role of receptor activator of nuclear factor-κB ligand and osteoprotegerin in bone cell biology. J Mol Med 2001; 79: 24353.
  • 10
    Kostenuik PJ, Shalhoub V. Osteoprotegerin: a physiological and pharmacological inhibitor of bone resorption. Curr Pharm Des 2001; 7: 61335.
  • 11
    Hsu H, Lacey DL, Dunstan CR, Solovyev I, Colombero A, Timms E, et al. 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: 35405.
  • 12
    Kong YY, Boyle WJ, Penninger JM. Osteoprotegerin ligand: a regulator of immune responses and bone physiology. Immunol Today 2000; 21: 495502.
  • 13
    Anderson DM, Maraskovsky E, Billingsley WL, Dougall WC, Tometsko ME, Roux ER, et al. A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic cell function. Nature 1997; 390: 1759.
  • 14
    Li J, Sarosi I, Yan X-Q, Morony S, Capparelli C, Tan HL, et al. 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 2000; 97: 156671.
  • 15
    Lacey DL, Timms E, Tan HL, Kelley MJ, Dunstan CR, Burgess T, et al. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 1998; 93: 16576.
  • 16
    Yasuda H, Shima N, Nakagawa N, Yamaguchi K, Kinosaki M, Mochizuki S, et al. Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci U S A 1998; 95: 3597602.
  • 17
    Wong BR, Josien R, Lee SY, Sauter B, Li HL, Steinman RM, et al. 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: 207580.
  • 18
    Lum L, Wong BR, Josien R, Becherer JD, Erdjument-Bromage H, Schlondorff J, et al. Evidence for a role of tumor necrosis factor-α (TNF-α)-converting enzyme-like protease in shedding of TRANCE, a TNF family member involved in osteoclastogenesis and dendritic cell survival. J Biol Chem 1999; 274: 136138.
  • 19
    Wong BR, Rho J, Arron J, Robinson E, Orlinick J, Chao M, et al. TRANCE is a novel ligand of the tumor necrosis receptor family that activates c-jun N-terminal kinase in T cells. J Biol Chem 1997; 272: 251904.
  • 20
    Kong YY, Feige U, Sarosi I, Bolon B, Tafuri A, Morony S, et al. Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand. Nature 1999; 402: 3049.
  • 21
    Lacey DL, Tan HL, Lu J, Kaufman S, Van G, Qiu WR, et al. Osteoprotegerin ligand modulates murine osteoclast survival in vitro and in vivo. Am J Pathol 2000; 157: 43548.
  • 22
    Kong YY, Yoshida H, Sarosi I, Tan HL, Timms E, Capparelli C, et al. OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph node organogenesis. Nature 1999; 397: 31523.
  • 23
    Kim N, Odgren PR, Kim DK, Marks SCJ, Choi Y. Diverse roles of the tumor necrosis factor family member TRANCE in skeletal physiology revealed by TRANCE deficiency and partial rescue by a lymphocyte-expressed TRANCE transgene. Proc Natl Acad Sci U S A 2000; 97: 1090510.
  • 24
    Yasuda H, Shima N, Nakagawa N, Mochizuki SI, Yano K, Fujise N, et al. Identity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): a mechanism by which OPG/OCIF inhibits osteoclastogenesis in vitro. Endocrinology 1998; 139: 132937.
  • 25
    Simonet WS, Lacey DL, Dunstan CR, Kelley M, Chang MS, Luethy R, et al. Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 1997; 89: 30919.
  • 26
    Yun TJ, Chaudhary PM, Shu GL, Frazer JK, Ewings MK, Schwartz SM, et al. OPG/FDCR-1, a TNF receptor family member, is expressed in lymphoid cells and is up-regulated by ligating CD40. J Immunol 1998; 161: 611321.
  • 27
    Kwon BS, Wang S, Udagawa N, Haridas V, Lee ZH, Kim KK, et al. TR1, a new member of the tumor necrosis factor receptor superfamily, induces fibroblast proliferation and inhibits osteoclastogenesis and bone resorption. FASEB J 1998; 12: 84554.
  • 28
    Tomoyasu A, Goto M, Fujise N, Mochizuki S, Yasuda H, Morinaga T, et al. Characterization of monomeric and homodimeric forms of osteoclastogenesis inhibitory factor. Biochem Biophys Res Commun 1998; 245: 3827.
  • 29
    Yamaguchi K, Kinosaki M, Goto M, Kobayashi F, Tsuda E, Morinaga T, et al. Characterization of structural domains of human osteoclastogenesis inhibitory factor. J Biol Chem 1998; 273: 511723.
  • 30
    Min H, Morony S, Sarosi I, Dunstan CR, Capparelli C, Scully S, et al. Osteoprotegerin reverses osteoporosis by inhibiting endosteal osteoclasts and prevents vascular calcification by blocking a process resembling osteoclastogenesis. J Exp Med 2000; 192: 46374.
  • 31
    Bucay N, Sarosi I, Dunstan CR, Morony S, Tarpley J, Capparelli C, et al. Osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification. Genes Dev 1998; 12: 12608.
  • 32
    Lee ZH, Kwack K, Kim KK, Lee SH, Kim HH. Activation of c-Jun N-terminal kinase and activator protein 1 by receptor activator of NF-κB. Mol Pharmacol 2000; 58: 153645.
  • 33
    Matsumoto M, Sudo T, Saito T, Osada H, Tsujimoto M. Involvement of p38 mitogen-activated protein kinase signaling pathway in osteoclastogenesis mediated by receptor activator of NF-κB ligand (RANKL). J Biol Chem 2000; 275: 3115561.
  • 34
    Arron JR, Vologodskaia M, Wong BR, Naramura M, Kim N, Gu H, et al. A positive regulatory role for Cbl family proteins in tumor necrosis factor-related activation-induced cytokine (TRANCE) and CD40L-mediated Akt activation. J Biol Chem 2001; 276: 300117.
  • 35
    Zhang YH, Heulsmann A, Tondravi MM, Mukherjee A, Abu-Amer Y. Tumor necrosis factor-α (TNF) stimulates RANKL-induced osteoclastogenesis via coupling of TNF type 1 receptor and RANK signaling pathways. J Biol Chem 2001; 276: 5638.
  • 36
    Udagawa N, Takahashi N, Yasuda H, Mizuno A, Itoh K, Ueno Y, et al. Osteoprotegerin produced by osteoblasts is an important regulator in osteoclast development and function. Endocrinology 2000; 141: 347884.
  • 37
    Shalhoub V, Faust J, Boyle WJ, Dunstan CR, Kelley M, Kaufman S, et al. Osteoprotegerin and osteoprotegerin ligand effects on osteoclast formation from human peripheral blood mononuclear cell precursors. J Cell Biochem 1999; 72: 25161.
  • 38
    Campagnuolo G, Bolon B, Feige U. Kinetics of bone protection by recombinant osteoprotegerin therapy in Lewis rats with adjuvant arthritis. Arthritis Rheum 2002; 46: 192636.
  • 39
    Jimi E, Akiyama S, Tsurukai T, Okahashi N, Kobayashi K, Udagawa N, et al. Osteoclast differentiation factor acts as a multifunctional regulator in murine osteoclast differentiation and function. J Immunol 1999; 163: 43442.
  • 40
    Hakeda Y, Kobayashi Y, Yamaguchi K, Yasuda H, Tsuda E, Higashio K, et al. Osteoclastogenesis inhibitory factor (OCIF) directly inhibits bone-resorbing activity of isolated mature osteoclasts. Biochem Biophys Res Commun 1998; 251: 796801.
  • 41
    Tsukii K, Shima N, Mochizuki S, Yamaguchi K, Kinosaki M, Yano K, et al. Osteoclast differentiation factor mediates an essential signal for bone resorption induced by 1 α,25-dihydroxyvitamin D3, prostaglandin E2, or parathyroid hormone in the microenvironment of bone. Biochem Biophys Res Commun 1998; 246: 33741.
  • 42
    Akatsu T, Murakami T, Ono K, Nishikawa M, Tsuda E, Mochizuki SI, et al. Osteoclastogenesis inhibitory factor exhibits hypocalcemic effects in normal mice and in hypercalcemic nude mice carrying tumors associated with humoral hypercalcemia of malignancy. Bone 1998; 23: 4958.
  • 43
    Yamamoto M, Murakami T, Nishikawa M, Tsuda E, Mochizuki S, Higashio K, et al. Hypocalcemic effect of osteoclastogenesis inhibitory factor/osteoprotegerin in the thyroparathyroidectomized rat. Endocrinology 1998; 139: 40125.
  • 44
    Akatsu T, Murakami T, Nishikawa M, Ono K, Shinomiya N, Tsuda E, et al. Osteoclastogenesis inhibitory factor suppresses osteoclast survival by interfering in the interaction of stromal cells with osteoclasts. Biochem Biophys Res Commun 1998; 250: 22934.
  • 45
    Murakami T, Yamamoto M, Ono K, Nishikawa M, Nagata N, Motoyoshi K, et al. Transforming growth factor-β1 increases mRNA levels of osteoclastogenesis inhibitory factor in osteoblastic/stromal cells and inhibits the survival of murine osteoclast-like cells. Biochem Biophys Res Commun 1998; 252: 74752.
  • 46
    Bolon B, Campagnuolo G, Feige U. Duration of bone protection afforded by a single injection of recombinant osteoprotegerin (OPG) in male Lewis rats with adjuvant arthritis. Cell Mol Life Sci 2002; 59: 156976.
  • 47
    Malyankar UM, Scatena M, Suchland KL, Yun TJ, Clark EA, Giachelli CM. Osteoprotegerin is an αvβ3-induced, NF-κB-dependent survival factor for endothelial cells. J Biol Chem 2000; 275: 2095962.
  • 48
    Price PA, June HH, Buckley JR, Williamson MK. Osteoprotegerin inhibits artery calcification induced by warfarin and by vitamin D. Arterioscler Thromb Vasc Biol 2001; 21: 16106.
  • 49
    Hak AE, Pols HA, van Hemert AM, Hofman A, Witteman JC. Progression of aortic calcification is associated with metacarpal bone loss during menopause: a population-based longitudinal study. Arterioscler Thromb Vasc Biol 2000; 20: 192631.
  • 50
    Fata JE, Kong YY, Li J, Sasaki T, Irie-Sasaki J, Moorehead RA, et al. The osteoclast differentiation factor osteoprotegerin-ligand is essential for mammary gland development. Cell 2000; 103: 4150.
  • 51
    Theill LE, Boyle WJ, Penninger JM. RANK-L and RANK: T cells, bone loss, and mammalian evolution. Annu Rev Immunol 2002; 20: 795823.
  • 52
    Emery JG, McDonnell P, Burke MB, Deen KC, Lyn S, Silverman C, et al. Osteoprotegerin is a receptor for the cytotoxic ligand TRAIL. J Biol Chem 1998; 273: 143637.
  • 53
    Nagai M, Sato N. Reciprocal gene expression of osteoclastogenesis inhibitory factor and osteoclast differentiation factor regulates osteoclast formation. Biochem Biophys Res Commun 1999; 257: 71923.
  • 54
    Morony S, Capparelli C, Lee R, Shimamoto G, Boone T, Lacey DL, et al. A chimeric form of osteoprotegerin inhibits hypercalcemia and bone resorption induced by IL-1β, TNF-α, PTH, PTHrP, and 1,25(OH)2D3. J Bone Miner Res 1999; 14: 147885.
  • 55
    Hofbauer LC, Khosla S, Dunstan CR, Lacey DL, Spelsberg TC, Riggs BL. Estrogen stimulates gene expression and protein production of osteoprotegerin in human osteoblastic cells. Endocrinology 1999; 140: 436770.
  • 56
    Shevde NK, Bendixen AC, Dienger KM, Pike JW. Estrogens suppress RANK ligand-induced osteoclast differentiation via a stromal cell independent mechanism involving c-Jun repression. Proc Natl Acad Sci U S A 2000; 97: 782934.
  • 57
    Lindberg MK, Erlandsson M, Alatalo SL, Windahl S, Andersson G, Halleen JM, et al. Estrogen receptor α, but not estrogen receptor β, is involved in the regulation of the OPG/RANKL (osteoprotegerin/receptor activator of NF-κB ligand) ratio and serum interleukin-6 in male mice. J Endocrinol 2001; 171: 42533.
  • 58
    Saika M, Inoue D, Kido S, Matsumoto T. 17β-Estradiol stimulates expression of osteoprotegerin by a mouse stromal cell line, ST-2, via estrogen receptor-α. Endocrinology 2001; 142: 220512.
  • 59
    Hofbauer LC, Gori F, Riggs BL, Lacey DL, Dunstan CR, Spelsberg TC, et al. Stimulation of osteoprotegerin ligand and inhibition of osteoprotegerin production by glucocorticoids in human osteoblastic lineage cells: potential paracrine mechanisms of glucocorticoid-induced osteoporosis. Endocrinology 1999; 140: 43829.
  • 60
    Vidal NOA, Brändström H, Jonsson KB, Ohlssonn C. Osteoprotegerin mRNA is expressed in primary human osteoclast-like cells: down-regulation by glucocorticoids. J Endocrinol 1998; 159: 1915.
  • 61
    Hofbauer LC, Shui C, Riggs BL, Dunstan CR, Spelsberg TC, O'Brien T, et al. Effects of immunosuppressants on receptor activator of NF-κB ligand and osteoprotegerin production by human osteoblastic and coronary artery smooth muscle cells. Biochem Biophys Res Commun 2001; 280: 3349.
  • 62
    Quinn JM, Horwood NJ, Elliott J, Gillespie MT, Martin TJ. Fibroblastic stromal cells express receptor activator of NF-κB ligand and support osteoclast differentiation. J Bone Miner Res 2000; 15: 145966.
  • 63
    Hofbauer LC, Dunstan CR, Spelsberg TC, Riggs BL, Khosla S. Osteoprotegerin production by human osteoblast lineage cells is stimulated by vitamin D, bone morphogenetic protein-2, and cytokines. Biochem Biophys Res Commun 1998; 250: 77681.
  • 64
    Hofbauer LC, Lacey DL, Dunstan CR, Spelsberg TC, Riggs BL, Khosla S. Interleukin-1β and tumor necrosis factor-α, but not interleukin-6, stimulate osteoprotegerin ligand gene expression in human osteoblastic cells. Bone 1999; 25: 2559.
  • 65
    Horwood NJ, Elliott J, Martin TJ, Gillespie MT. Osteotropic agents regulate the expression of osteoclast differentiation factor and osteoprotegerin in osteoblastic stromal cells. Endocrinology 1998; 139: 47436.
  • 66
    Kotake S, Udagawa N, Takahashi N, Matsuzaki K, Itoh K, Ishiyama S, et al. IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis. J Clin Invest 1999; 103: 134552.
  • 67
    Brändström H, Jonsson KB, Vidal O, Ljunghall S, Ohlsson C, Ljunggren Ö. Tumor necrosis factor-α and -β upregulate the levels of osteoprotegerin mRNA in human osteosarcoma MG-63 cells. Biochem Biophys Res Commun 1998; 248: 4547.
  • 68
    Takai H, Kanematsu M, Yano K, Tsuda E, Higashio K, Ikeda K, et al. Transforming growth factor-β stimulates the production of osteoprotegerin/osteoclastogenesis inhibitory factor by bone marrow stromal cells. J Biol Chem 1998; 273: 270916.
  • 69
    Haynes DR, Crotti TN, Loric M, Bain GI, Atkins GJ, Findlay DM. Osteoprotegerin and receptor activator of nuclear factor κB ligand (RANKL) regulate osteoclast formation by cells in the human rheumatoid arthritic joint. Rheumatology (Oxford) 2001; 40: 62330.
  • 70
    Shimizu S, Shiozawa S, Shiozawa K, Imura S, Fujita T. Quantitative histologic studies on the pathogenesis of periarticular osteoporosis in rheumatoid arthritis. Arthritis Rheum 1985; 28: 2531.
  • 71
    Gravallese EM, Harada Y, Wang JT, Gorn AH, Thornhill TS, Goldring SR. Identification of cell types responsible for bone resorption in rheumatoid arthritis and juvenile rheumatoid arthritis. Am J Pathol 1998; 152: 94351.
  • 72
    Takayanagi H, Iizuka H, Juji T, Nakagawa T, Yamamoto A, Miyazaki T, et al. Involvement of receptor activator of nuclear factor κB ligand/osteoclast differentiation factor in osteoclastogenesis from synoviocytes in rheumatoid arthritis. Arthritis Rheum 2000; 43: 25969.
  • 73
    Tsurukai T, Udagawa N, Matsuzaki K, Takahashi N, Suda T. Roles of macrophage-colony stimulating factor and osteoclast differentiation factor in osteoclastogenesis. J Bone Miner Res 2000; 18: 17784.
  • 74
    Makhluf HA, Mueller SM, Mizuno S, Glowacki J. Age-related decline in osteoprotegerin expression by human bone marrow cells cultured in three-dimensional collagen sponges. Biochem Biophys Res Commun 2000; 268: 66972.
  • 75
    Yano K, Tsuda E, Washida N, Kobayashi F, Goto M, Harada A, et al. Immunological characterization of circulating osteoprotegerin/osteoclastogenesis inhibitory factor: Increased serum concentrations in postmenopausal women with osteoporosis. J Bone Miner Res 1999; 14: 51827.
  • 76
    Lipton A, Ali SM, Leitzel K, Chinchilli V, Witters L, Engle L, et al. Serum osteoprotegerin (OPG) levels in healthy controls and cancer patients. Clin Cancer Res 2002; 8: 230610.
  • 77
    Seck T, Diel I, Bismar H, Ziegler R, Pfeilschifter J. Serum parathyroid hormone, but not menopausal status, is associated with the expression of osteoprotegerin and RANKL mRNA in human bone samples. Eur J Endocrinol 2001; 145: 199205.
  • 78
    Toritsuka Y, Nakamura N, Lee SB, Hashimoto J, Yasui N, Shino K, et al. Osteoclastogenesis in iliac bone marrow of patients with rheumatoid arthritis. J Rheumatol 1997; 24: 16906.
  • 79
    Hofbauer LC, Neubauer A, Heufelder AE. Receptor activator of nuclear factor-κB ligand and osteoprotegerin: potential implications for the pathogenesis and treatment of malignant bone diseases. Cancer 2001; 92: 46070.
  • 80
    Atkins GJ, Haynes DR, Graves SE, Evdokiou A, Hay S, Bouralexis S, et al. Expression of osteoclast differentiation signals by stromal elements of giant cell tumors. J Bone Miner Res 2000; 15: 6409.
  • 81
    Croucher PI, Shipman CM, Lippitt J, Perry M, Asosingh K, Hijzen A, et al. Osteoprotegerin inhibits the development of osteolytic bone disease in multiple myeloma. Blood 2001; 98: 353440.
  • 82
    Brown JM, Vessella RL, Kostenuik PJ, Dunstan CR, Lange PH, Corey E. Serum osteoprotegerin levels are increased in patients with advanced prostate cancer. Clin Cancer Res 2001; 7: 297783.
  • 83
    Pettit AR, Ji H, von Stechow D, Muller R, Goldring SR, Choi YW, et al. TRANCE/RANKL knockout mice are protected from bone erosion in a serum transfer model of arthritis. Am J Pathol 2001; 159: 168999.
  • 84
    Redlich K, Hayer S, Maier A, Dunstan CR, Tohidast-Akrad M, Lang S, et al. Tumor necrosis factor α–mediated joint destruction is inhibited by targeting osteoclasts with osteoprotegerin. Arthritis Rheum 2002; 46: 78592.
  • 85
    Romas E, Sims NA, Hards D, Lindsay M, Ryan PFJ, Quinn JA, et al. Fc-osteoprotegerin fusion protein (Fc-OPG) reduces osteoclast numbers and prevents bone destruction in rats with collagen-induced arthritis. Arthritis Rheum 2001; 44 Suppl 9: S267.
  • 86
    Chu CQ, Field M, Allard S, Abney E, Feldmann M, Maini RN. Detection of cytokines at the cartilage/pannus junction in patients with rheumatoid arthritis: implications for the role of cytokines in cartilage destruction and repair. Br J Rheumatol 1992; 31: 65361.
  • 87
    Kobayashi K, Takahashi N, Jimi E, Udagawa N, Takami M, Kotake S, et al. Tumor necrosis factor α stimulates osteoclast differentiation by a mechanism independent of the ODF/RANKL-RANK interaction. J Exp Med 2000; 191: 27586.
  • 88
    Suda T, Kobayashi K, Jimi E, Udagawa N, Takahashi N. The molecular basis of osteoclast differentiation and activation. Novartis Found Symp 2001; 232: 23547; discussion 247–50.
  • 89
    Fuller K, Fox SW, Kirstein B, Chambers TJ. Osteoclast regulation by TNF-α occurs through distinct mechanisms in vitro versus in vivo. J Bone Miner Res 2001; 16 Suppl 1: S377.
  • 90
    Collin-Osdoby P, Rothe L, Anderson F, Nelson M, Maloney W, Osdoby P. Receptor activator of NF-κB and osteoprotegerin expression by human microvascular endothelial cells, regulation by inflammatory cytokines, and role in human osteoclastogenesis. J Biol Chem 2001; 276: 2065972.
  • 91
    Horwood NJ, Kartsogiannis V, Quinn JM, Romas E, Martin TJ, Gillespie MT. Activated T lymphocytes support osteoclast formation in vitro. Biochem Biophys Res Commun 1999; 265: 14450.
  • 92
    Xu LX, Kukita T, Nakano Y, Yu H, Hotokebuchi T, Kuratani T, et al. Osteoclasts in normal and adjuvant arthritis bone tissues express the mRNA for both type I and II interleukin-1 receptors. Lab Invest 1996; 75: 67787.
  • 93
    Kimble RB, Srivastava S, Ross FP, Matayoshi A, Pacifici R. Estrogen deficiency increases the ability of stromal cells to support murine osteoclastogenesis via an interleukin-1 and tumor necrosis factor-mediated stimulation of macrophage colony-stimulating factor production. J Biol Chem 1996; 271: 288907.
  • 94
    Gravallese EM, Manning C, Tsay A, Naito A, Pan C, Amento E, et al. Synovial tissue in rheumatoid arthritis is a source of osteoclast differentiation factor. Arthritis Rheum 2000; 43: 2508.
  • 95
    Bekker PJ, Holloway D, Nakanishi A, Arrighi HM, Leese PT, Dunstan CR. The effect of a single dose of osteoprotegerin in postmenopausal women. J Bone Miner Res 2001; 16: 34860.
  • 96
    Lomaga MA, Yeh WC, Sarosi I, Duncan GS, Furlonger C, Ho A, et al. TRAF6 deficiency results in osteopetrosis and defective interleukin-1, CD40, and LPS signaling. Genes Dev 1999; 13: 101524.
  • 97
    Boyce BF, Hughes DE, Wright KR, Xing LP, Dai AH. Recent advances in bone biology provide insight into the pathogenesis of bone diseases. Lab Invest 1999; 79: 8394.
  • 98
    Wang ZQ, Ovitt C, Grigoriadis A, Mohle-Steinlein U, Ruther U, Wagner EF. Bone and haematopoietic defects in mice lacking c-fos. Nature 1992; 360: 7415.
  • 99
    Matsuo K, Owens JM, Tonko M, Elliott C, Chambers TJ, Wagner EF. Fos/1 is a transcriptional target of c-Fos during osteoclast differentiation. Nat Genet 2000; 24: 1847.
  • 100
    Brändström H, Björkman T, Ljunggren Ö. Regulation of osteoprotegerin secretion from primary cultures of human bone marrow stromal cells. Biochem Biophys Res Commun 2001; 280: 8315.
  • 101
    O'Brien CA, Gubrij I, Lin SC, Saylors RL, Manolagas SC. STAT3 activation in stromal/osteoblastic cells is required for induction of the receptor activator of NF-κB ligand and stimulation of osteoclastogenesis by gp130-utilizing cytokines or interleukin-1 but not 1,25-dihydroxyvitamin D3 or parathyroid hormone. J Biol Chem 1999; 274: 193018.
  • 102
    Weitzmann MN, Cenci S, Rifas L, Brown C, Pacifici R. Interleukin-7 stimulates osteoclast formation by up-regulating the T-cell production of soluble osteoclastogenic cytokines. Blood 2000; 96: 18738.
  • 103
    Makiishi-Shimobayashi C, Tsujimura T, Iwasaki T, Yamada N, Sugihara A, Okamura H, et al. Interleukin-18 up-regulates osteoprotegerin expression in stromal/osteoblastic cells. Biochem Biophys Res Commun 2001; 281: 3616.
  • 104
    Brändström H, Jonsson KB, Ohlsson C, Vidal O, Ljunghall S, Ljunggren Ö. Regulation of osteoprotegerin mRNA levels by prostaglandin E2 in human bone marrow stromal cells. Biochem Biophys Res Commun 1998; 247: 33841.
  • 105
    Quinn JM, Itoh K, Udagawa N, Häusler K, Yasuda H, Shima N, et al. Transforming growth factor β affects osteoclast differentiation via direct and indirect actions. J Bone Miner Res 2001; 16: 178794.
  • 106
    Thirunavukkarasu K, Miles RR, Halladay DL, Yang X, Galvin RJS, Chandrasekhar S, et al. Stimulation of osteoprotegerin (OPG) gene expression by transforming growth factor-β (TGF-β). J Biol Chem 2001; 276: 3624150.
  • 107
    Lee SK, Lorenzo JA. Parathyroid hormone stimulates TRANCE and inhibits osteoprotegerin messenger ribonucleic acid expression in murine bone marrow cultures: correlation with osteoclast-like cell formation. Endocrinology 1999; 140: 355261.
  • 108
    Itoh K, Udagawa N, Matsuzaki K, Takami M, Amano H, Shinki T, et al. Importance of membrane- or matrix-associated forms of M-CSF and RANKL/ODF in osteoclastogenesis supported by SaOS-4/3 cells expressing recombinant PTH/PTHrP receptors. J Bone Miner Res 2000; 15: 176675.
  • 109
    Ma YL, Cain RL, Halladay DL, Yang X, Zeng Q, Miles RR, et al. Catabolic effects of continuous human PTH (1–38) in vivo is associated with sustained stimulation of RANKL and inhibition of osteoprotegerin and gene-associated bone formation. Endocrinology 2001; 142: 404754.
  • 110
    Thomas RJ, Guise TA, Yin JJ, Elliott J, Horwood NJ, Martin TJ, et al. Breast cancer cells interact with osteoblasts to support osteoclast formation. Endocrinology 1999; 140: 44518.
  • 111
    Hofbauer LC, Hicok KC, Chen D, Khosla S. Regulation of osteoprotegerin production by androgens and anti-androgens in human osteoblastic lineage cells. Eur J Endocrinol 2002; 147: 26973.
  • 112
    Kotake S, Udagawa N, Hakoda M, Mogi M, Yano K, Tsuda E, et al. Activated human T cells directly induce osteoclastogenesis from human monocytes: possible role of T cells in bone destruction in rheumatoid arthritis patients. Arthritis Rheum 2001; 44: 100312.
  • 113
    Capparelli C, Kostenuik PJ, Morony S, Starnes C, Weimann B, Van G, et al. Osteoprotegerin prevents and reverses hypercalcemia in a murine model of humoral hypercalcemia of malignancy. Cancer Res 2000; 60: 7837.
  • 114
    Honore P, Luger NM, Sabino MA, Schwei MJ, Rogers SD, Mach DB, et al. Osteoprotegerin blocks bone cancer-induced skeletal destruction, skeletal pain and pain-related neurochemical reorganization of the spinal cord. Nat Med 2000; 6: 5218.
  • 115
    Luger NM, Honore P, Sabino MA, Schwei MJ, Rogers SD, Mach DB, et al. Osteoprotegerin diminishes advanced bone cancer pain. Cancer Res 2001; 61: 403847.
  • 116
    Kostenuik PJ, Capparelli C, Morony S, Adamu S, Shimamoto G, Shen V, et al. OPG and PTH-(1–34) have additive effects on bone density and mechanical strength in osteopenic ovariectomized rats. Endocrinology 2001; 142: 4295304.
  • 117
    Teng YT, Nguyen H, Gao X, Kong YY, Gorczynski RM, Singh B, et al. Functional human T-cell immunity and osteoprotegerin ligand control alveolar bone destruction in peridontal infection. J Clin Invest 2000; 106: R5967.
  • 118
    Bateman TA, Dunstan CR, Ferguson VL, Lacey DL, Ayers RA, Simske SJ. Osteoprotegerin mitigates tail suspension-induced osteopenia. Bone 2000; 26: 4439.
  • 119
    Bateman TA, Dunstan CR, Lacey DL, Ferguson VL, Ayers RA, Simske SJ. Osteoprotegerin ameliorates sciatic nerve crush induced bone loss. J Ortho Res 2001; 19: 51823.
  • 120
    Morony S, Capparelli C, Sarosi I, Lacey DL, Dunstan CR, Kostenuik PJ. Osteoprotegerin inhibits osteolysis and decreases skeletal tumor burden in syngeneic and nude mouse models of experimental bone metastasis. Cancer Res 2001; 61: 44326.
  • 121
    Bolon B, Carter C, Daris M, Morony S, Capparelli C, Hsieh A, et al. Adenoviral delivery of osteoprotegerin ameliorates bone resorption in a mouse ovariectomy model of osteoporosis. Mol Ther 2001; 3: 197205.