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The Mechanisms of Bone Loss due to Estrogen Deficiency: Possible Role of Increased B-Lymphopoiesis in Bone Resorption

  • Conference paper
Hormone Replacement Therapy and Osteoporosis

Part of the book series: Ernst Schering Research Foundation Workshop ((3368,volume 4))

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Abstract

An estrogen deficiency, caused by either menopause or removal of the ovaries, results in a marked bone loss by increased osteoclastic bone resorption. The pathologic bone loss in this condition can be restored by estrogen replacement therapy, but the mechanism underlying this phenomenon remains unknown. There appears to be a close relationship between bone remodeling and hemopoiesis in bone marrow (Suda et al. 1992). Osteoclast progenitors are thought to be of hemopoietic origin, and they are recruited from bone marrow (Suda et al. 1992). It is also suggested that several cytokines produced by bone marrow cells affect bone remodeling (Suda et al. 1992). Recent studies indicated the possible involvement of bone-resorbing cytokines such as interleukin (IL)-1, IL-6, and tumor necrosis factor α (TNFα) in bone loss due to estrogen deficiency.

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References

  • Ammann P, Rizzoli R, Bonjour J, Bourrin S, Meyer JM, Vassalli P, Garcia I (1997) Transgenic mice expressing soluble tumor necrosis factor-receptor are protected against bone loss caused by estrogen deficiency. J Clin Invest 99: 1699–1703

    Article  PubMed  CAS  Google Scholar 

  • Anderson DM, Maraskovsky E, Billingsley WL, Dougall WC, Tometsko ME, Roux ER, Teepe MC, DuBose RF, Cosman D, Galibert L (1997) A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function. Nature 390: 175–179

    Article  PubMed  CAS  Google Scholar 

  • Asami T, Inada M, Mizunuma H, Ibuki Y, Miyaura C (1999) Expression of osteoclast differentiation factor (ODF/RANKL/OPGL) in trabecular bone and bone marrow B-lymphocytes in OVX mice. J Bone Miner Res 14:S 152

    Article  Google Scholar 

  • Black LJ, Sato M, Rowley ER, Magee DE, Bekele A, Williams DC, Cullinian GJ, Bendele R, Kauffman RF, Bensch WR, Frolik CA, Termine JD, Bryant HU (1994) Raloxifene (LY139481 HC1) prevents bone loss and reduces serum cholesterol without uterine hypertrophy in ovariectomized rats. J Clin Invest 93: 63–69

    Article  PubMed  CAS  Google Scholar 

  • Chaki O, Miyaura C, Seo H, Gorai I, Minaguchi H, Suda T (1996) Androgen deficiency stimulates B-lymphopoiesis in bone marrow and induces bone loss in male mice: Comparison of the effects of estrogen and androgen. In: Papapoulos SE, Lips P, Pols HAP, Johnston CC, Delmas PD (eds) Osteoporosis 1996. Proceeding of the 1996 World Congress on Osteoporosis, Elsevier, Amsterdam, pp 37–41

    Google Scholar 

  • Girasole G, Jilka RL, Passeri G, Boswell S, Boder G, Williams DC, Manolagas SC (1992) 17(3-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 9: 883–891

    Google Scholar 

  • Ishimi Y, Miyaura C, Ohmura M, Onoe Y, Sato T, Uchiyama Y, Ito M, Wang X, Suda T, Ikegami S (1999) Selective effects of genistein, a soybean isoflavone, on B-lymphopoiesis and bone loss caused by estrogen deficiency. Endocrinology 140: 1893–1900

    Article  PubMed  CAS  Google Scholar 

  • Jilka RL, Hangoc G, Girasole G, Passeri G, Williams DC, Abrams JS, Boyce B, Broxmeyer H, Manolagas SC (1992) Increased osteoclast development after estrogen loss: Mediation by interleukin-6. Science 257: 88–91

    Article  PubMed  CAS  Google Scholar 

  • Kawaguchi H, Pilbeam CC, Vargas SJ, Morse EE, Lorenzo JA, Raisz LG (1995) Ovariectomy enhances and estrogen replacement inhibits the activity of bone marrow factors that stimulate prostaglandin production in cultured mouse calvariae. J Clin Invest 96: 539–548

    Article  PubMed  CAS  Google Scholar 

  • Kimble RB, Vannice JL, Bloedow DC, Thompson RC, Hopfer W, Kung VT, Brownfield C, Pacifici R (1994) Interleukin-1 receptor antagonist decreases bone loss and bone resorption in ovariectomized rats. J Clin Invest 93: 1959–1967

    Article  PubMed  CAS  Google Scholar 

  • 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: 2397–2406

    Article  PubMed  CAS  Google Scholar 

  • Lacey DL, Timms E, Tan HL, Kelley MJ, Dunstan CR, Burgess T, Elliott R, Colombero A, Elliott G, Scully S, Hsu H, Sullivan J, Hawkins N, Davy E, Capparelli C, Eli A, Qian YX, Kaufman S, Sarosi I, Shalhoub V, Senaldi G, Guo J, Delaney J, Boyle WJ (1998) Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 93: 165–176

    Article  PubMed  CAS  Google Scholar 

  • Lee G, Namen AE, Gillis S, Ellingsworth LR, Kincade PW (1989) Normal B cell precursors responsive to recombinant murine IL-7 and inhibition of IL-7 activity by transforming growth factor-(3. J Immunol 142: 3875–3883

    PubMed  CAS  Google Scholar 

  • Masuzawa T, Miyaura C, Onoe Y, Kusano K, Ohta H, Nozawa S, Suda T (1994) Estrogen deficiency stimulates B lymphopoiesis in mouse bone marrow. J Clin Invest 94: 1090–1097

    Article  PubMed  CAS  Google Scholar 

  • Medina KL, Smithson G, Kincade PW (1993) Suppression of B lymphopoiesis during normal pregnancy. J Exp Med 178: 1507–1515

    Article  PubMed  CAS  Google Scholar 

  • Miyaura C, Kusano K, Masuzawa T, Chaki O, Onoe Y, Aoyagi M, Sasaki T, Tamura T, Koishihara Y, Ohsugi Y, Suda T (1995) Endogenous bone-resorbing factors in estrogen deficiency: Cooperative effects of IL-1 and IL-6. J Bone Miner Res 10: 1365–1373

    Article  PubMed  CAS  Google Scholar 

  • Miyaura C, Onoe Y, Inada M, Maki K, Ikuta K, Ito M, Suda T (1997) Increased B-Iymphopoiesis by interleukin 7 induces bone loss in mice with intact ovarian function: Similarity to estrogen deficiency. Proc Natl Acad Sci USA 94: 9360–9365

    Google Scholar 

  • Morrissey PJ, Conlon P, Charrier K, Braddy S, Alpert A, Williams D, Namen AE, Mochizuki D (1991) Administration of IL-7 to normal mice stimulates B-lymphopoiesis and peripheral lymphadenopathy. J Immunol 147: 561568

    Google Scholar 

  • Namen AE, Lupton S, Hjerrild K, Wignall J, Mochizuki DY, Schmierer A, Mosley B, March CJ, Urdal D, Gillis S, Cosman D, Goodwin RG (1988) Stimulation of B cell progenitors by cloned murine IL-7. Nature 333: 571–573

    Article  PubMed  CAS  Google Scholar 

  • Onoe Y, Miyaura C, Kaminakayashiki T, Nagai Y, Noguchi K, Chen QR, Seo H, Ohta H, Nozawa S, Kudo I, Suda T (1996) IL-13 and IL-4 inhibit bone resorption by suppressing cyclooxygenase-2-dependent prostaglandin synthesis in osteoblasts. J Immunol 156: 758–764

    PubMed  CAS  Google Scholar 

  • Onoe Y, Miyaura C, Ito M, Ohta H, Nozawa S, Suda T (in press) Comparative effects of estrogen and raloxifene on B-lymphopoiesis and bone loss induced by sex steroid deficiency in mice. J Bone Miner Res

    Google Scholar 

  • Pacifici R, Brown C, Puscheck E, Friedrich E, Slatopolsky E, Maggio D, McCracken R, Avioli LV (1991) Effect of surgical menopause and estrogen replacement on cytokine release from human blood mononuclear cells. Proc Natl Acad Sci USA 88: 5134–5138

    Article  PubMed  CAS  Google Scholar 

  • Poli V, Balena R, Fattori E, Markatos A, Yamamoto M, Tanaka H, Ciliberto G, Rodan GA, Costantini F (1994) Interleukin-6 deficient mice are protected from bone loss caused by estrogen depletion. EMBO J 13: 1189–1196

    PubMed  CAS  Google Scholar 

  • Smithson G, Medina K, Ponting 1, Kincade PW (1995) Estrogen suppresses stromal cell-dependent lymphopoiesis in culture. J Immunol 155: 3409–3417

    PubMed  CAS  Google Scholar 

  • Suda T, Takahashi N, Martin TJ (1992) Modulation of osteoclast differentiation. Endocr Rev 13: 66–80

    PubMed  CAS  Google Scholar 

  • Suda T, Takahashi N, Udagawa N, Jimi E, Gillespie MT, Martin TJ (1999) Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families. Endocrine Rev 20: 345–357

    Article  CAS  Google Scholar 

  • Tai H, Miyaura C, Pilbeam CC, Tamura T, Ohsugi Y, Koishihara Y, Kubodera N, Kawaguchi H, Raisz LG, Suda T (1997) Transcriptional induction of cyclooxygenase-2 in osteoblasts is involved in interleukin-6-induced osteoclast formation. Endocrinology 138: 2372–2379

    Article  PubMed  CAS  Google Scholar 

  • Wilson CA, Mrose SA, Thomas DW (1995) Enhanced production of B lymphopoiesis after castration. Blood 85: 1535–1539

    PubMed  CAS  Google Scholar 

  • Wong BR, Rho J, Anon J, Robinson E, Orlinick J, Chao M, Kalachikov S, Cayani E, Bartlett FS III, Frankel WN, Lee SY, Choi Y (1997) TRANCE is a novel ligand of the tumor necrosis factor receptor family that activates c-Jun N-terminal kinase in T cells. J Biol Chem 272: 25190–25194

    Article  PubMed  CAS  Google Scholar 

  • Yasuda H, Shima N, Nakagawa N, Yamaguchi K, Kinosaki M, Mochizuki S, Tomoyasu A, Yano K, Goto M, Murakami A, Tsuda E, Morinaga T, Higashio K, Udagawa N, Takahashi N, Suda T (1998) Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci USA 95: 3597–3602

    Article  PubMed  CAS  Google Scholar 

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Authors
  1. C. Miyaura
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Editors and Affiliations

  1. Teikyo Heisei Junior College, 6-29-1 Ichiharadai, 290-0192, Ichihara-shi, Chiba, Japan

    J. Kato

  2. Minaguchi Hospital, 1-7-7 Minamicho, 180-0003, Kichijoji Musashino-shi, Tokyo, Japan

    H. Minaguchi

  3. Preclinical Development Department, Nihon Schering K.K., 6-64, Nishimiyahara 2-Chome, 532-0004, Yodogawa-ku, Osaka-shi, Osaka, Japan

    Y. Nishino

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© 2000 Springer-Verlag Berlin Heidelberg

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Miyaura, C. (2000). The Mechanisms of Bone Loss due to Estrogen Deficiency: Possible Role of Increased B-Lymphopoiesis in Bone Resorption. In: Kato, J., Minaguchi, H., Nishino, Y. (eds) Hormone Replacement Therapy and Osteoporosis. Ernst Schering Research Foundation Workshop, vol 4. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-04021-8_11

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  • DOI: https://doi.org/10.1007/978-3-662-04021-8_11

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-04023-2

  • Online ISBN: 978-3-662-04021-8

  • eBook Packages: Springer Book Archive

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