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Knochenstoffwechsel

Molekulare Mechanismen

Bone metabolism: molecular mechanisms

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Zeitschrift für Rheumatologie Aims and scope Submit manuscript

Zusammenfassung

Um den individuellen Belastungen gerecht zu werden, ist das Skelettsystem einem ständigen Umbauprozess unterworfen. Der Knochenstoffwechsel garantiert eine optimale Struktur des Knochens. Dabei sind Osteoblasten für den Aufbau, Osteoklasten für den Abbau des Knochens zuständig. Ein fein abgestimmtes Zusammenspiel von molekularen Mechanismen führt mittels Zytokinen, Hormonen und Wachstumsfaktoren zu einer Homöostase des Knochenstoffwechsels. Bei Störungen dieses Prozesses kommt es durch verstärkten Knochenaufbau zur Osteopetrose, durch verstärkten Abbau zur Osteoporose. Der vorliegende Beitrag beschreibt die bekannten molekularen Mechanismen dieser Remodellingprozesse.

Abstract

In order to accommodate individual load, the skeletal system is in a continual state of change. Bone metabolism guarantees optimal bone structure. The osteoblasts are responsible for the synthesis and the osteoclasts for resorption of the bone. A finely adjusted interplay between molecular mechanisms leads, via cytokines, hormones and growth factors, to an homeostasis in bone metabolism. Disturbances of this process lead via increased bone resorption to osteoporosis, and via increased synthesis to osteopetrosis. This contribution describes the known molecular mechanisms in this remodelling process.

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Literatur

  1. Blumsohn A, Naylor KE, Timm W et al. (2003) Absence of marked seasonal change in bone turnover: a longitudinal and multicenter cross-sectional study. J Bone Miner Res 18: 1274–1281

    Article  PubMed  Google Scholar 

  2. Bord S, Ireland DC, Beavan SR, Compston JE (2003) The effects of estrogen on osteoprotegerin, RANKL, and estrogen receptor expression in human osteoblasts. Bone 32: 136–141

    Article  PubMed  CAS  Google Scholar 

  3. Boyle WJ, Simonet WS, Lacey DL (2003) Osteoclast differentiation and activation. Nature 423: 337–342

    Article  PubMed  CAS  Google Scholar 

  4. Cao X, Chen D (2005) The BMP signalling and in vivo bone formation. Gene 357: 1–8

    Article  PubMed  CAS  Google Scholar 

  5. Catrina AI, af Klint E, Ernestam S et al. (2006) Anti-tumor necrosis factor therapy increases synovial osteoprotegerin expression in rheumatoid arthritis. Arthritis Rheum 54: 76–81

    Article  PubMed  CAS  Google Scholar 

  6. Charatcharoenwitthaya N, Khosla S, Atkinson EJ et al. (2007) Effect of blockade of TNF-alpha and Interleukin-1 action on bone resorption in early postmenopausal women. J Bone Miner Res 22: 724–729

    Article  PubMed  CAS  Google Scholar 

  7. Cohen MM Jr (2006) The new bone biology: pathologic, molecular, and clinical correlates. Am J Med Genet A 140: 2646–2706

    PubMed  Google Scholar 

  8. Diarra D, Stolina M, Polzer K et al. (2007) Dickkopf-1 is a master regulator of joint remodeling. Nat Med 13: 156–163

    Article  PubMed  CAS  Google Scholar 

  9. Dobnig H, Hofbauer LC, Viereck V et al. (2006) Changes in the RANK ligand/osteoprotegerin system are correlated to changes in bone mineral density in bisphosphonate-treated osteoporotic patients. Osteoporos Int 17: 693–703

    Article  PubMed  CAS  Google Scholar 

  10. Glass DA, Karsenty G (2006) Molecular bases of the regulation of bone remodeling by the canonical Wnt signaling pathway. Curr Top Dev Biol 73: 43–84

    Article  PubMed  CAS  Google Scholar 

  11. Goldring SR (2003) Inflammatory mediators as essential elements in bone remodeling. Calcif Tissue Int 73: 97–100

    Article  PubMed  CAS  Google Scholar 

  12. Gravallese EM, Galson DL, Goldring SR, Auron PE (2001) The role of TNF-receptor family members and other TRAF-dependent receptors in bone resorption. Arthritis Res 3: 6–12

    Article  PubMed  CAS  Google Scholar 

  13. Hadjidakis DJ, Androulakis II (2006) Bone remodeling. Ann N Y Acad Sci 1092: 385–396

    Article  PubMed  CAS  Google Scholar 

  14. Hofbauer LC (2006) Pathophysiology of RANK ligand (RANKL) and osteoprotegerin (OPG). Ann Endocrinol (Paris) 67: 139–141

    Google Scholar 

  15. Hofbauer LC, Schoppet M (2004) Clinical implications of the osteoprotegerin/RANKL/RANK system for bone and vascular diseases. JAMA 292: 490–495

    Article  PubMed  CAS  Google Scholar 

  16. Kostenuik PJ (2005) Osteoprotegerin and RANKL regulate bone resorption, density, geometry and strength. Curr Opin Pharmacol 5: 618–625

    Article  PubMed  CAS  Google Scholar 

  17. Kotake S, Udagawa N, Takahashi N et al. (1999) IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis. J Clin Invest 103: 1345–1352

    PubMed  CAS  Google Scholar 

  18. Krishnan V, Bryant HU, Macdougald OA (2006) Regulation of bone mass by Wnt signaling. J Clin Invest 116: 1202–1209

    Article  PubMed  CAS  Google Scholar 

  19. Lacey DL, Timms E, Tan HL et al. (1998) Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 93: 165–176

    Article  PubMed  CAS  Google Scholar 

  20. Lam J, Takeshita S, Barker JE et al. (2000) TNF-alpha induces osteoclastogenesis by direct stimulation of macrophages exposed to permissive levels of RANK ligand. J Clin Invest 106: 1481–1488

    Article  PubMed  CAS  Google Scholar 

  21. Lange U, Teichmann J, Muller-Ladner U, Strunk J (2005) Increase in bone mineral density of patients with rheumatoid arthritis treated with anti-TNF-alpha antibody: a prospective open-label pilot study. Rheumatology (Oxford) 44: 1546–1548

    Google Scholar 

  22. Lee SK, Gardner AE, Kalinowski JF et al. (2006) RANKL-stimulated osteoclast-like cell formation in vitro is partially dependent on endogenous interleukin-1 production. Bone 38: 678–685

    Article  PubMed  CAS  Google Scholar 

  23. Li P, Schwarz EM, O’Keefe RJ et al. (2004) RANK signalling is not required for TNF-alpha-mediated increase in CD11(hi) osteoclast precursors but is essential for mature osteoclast formation in TNF-alpha-mediated inflammatory arthritis. J Bone Miner Res 19: 207–213

    Article  PubMed  CAS  Google Scholar 

  24. Liu XH, Kirschenbaum A, Yao S, Levine AC (2006) Interactive effect of interleukin-6 and prostaglandin E2 on osteoclastogenesis via the OPG/RANKL/RANK system. Ann N Y Acad Sci 1068: 225–233

    Article  PubMed  CAS  Google Scholar 

  25. Okamoto M, Murai J, Yoshikawa H, Tsumaki N (2006) Bone morphogenetic proteins in bone stimulate osteoclasts and osteoblasts during bone development. J Bone Miner Res 21: 1022–1033

    Article  PubMed  CAS  Google Scholar 

  26. Pasco JA, Kotowicz MA, Henry MJ et al. (2006) High-sensitivity C-reactive protein and fracture risk in elderly women. JAMA 296: 1353–1355

    Article  PubMed  CAS  Google Scholar 

  27. Ritchlin CT, Haas-Smith SA, Li P et al. (2003) Mechanisms of TNF-alpha- and RANKL-mediated osteoclastogenesis and bone resorption in psoriatic arthritis. J Clin Invest 111: 821–831

    Article  PubMed  CAS  Google Scholar 

  28. Sambrook P, Cooper C (2006) Osteoporosis. Lancet 367: 2010–2018

    Article  PubMed  CAS  Google Scholar 

  29. Sato K, Suematsu A, Okamoto K et al. (2006) Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction. J Exp Med 203: 2673–2682

    Article  PubMed  CAS  Google Scholar 

  30. Schett G, Kiechl S, Weger S et al. (2006) High-sensitivity C-reactive protein and risk of nontraumatic fractures in the Bruneck study. Arch Intern Med 166: 2495–2501

    Article  PubMed  CAS  Google Scholar 

  31. Seibel MJ (2006) Clinical application of biochemical markers of bone turnover. Arq Bras Endocrinol Metabol 50: 603–620

    PubMed  Google Scholar 

  32. Takayanagi H, Ogasawara K, Hida S et al. (2000) T-cell-mediated regulation of osteoclastogenesis by signalling cross-talk between RANKL and IFN-gamma. Nature 408: 600–605

    Article  PubMed  CAS  Google Scholar 

  33. Teitelbaum SL (2000) Bone resorption by osteoclasts. Science 289: 1504–1508

    Article  PubMed  CAS  Google Scholar 

  34. Dijke P ten (2006) Bone morphogenetic protein signal transduction in bone. Curr Med Res Opin (Suppl 1) 22: S7–S11

    Article  CAS  Google Scholar 

  35. Vis M, Havaardsholm EA, Haugeberg G et al. (2006) Evaluation of bone mineral density, bone metabolism, osteoprotegerin and RANKL serum levels during treatment with infliximab in patients with rheumatoid arthritis. Ann Rheum Dis 65: 1495–1499

    Article  PubMed  CAS  Google Scholar 

  36. Wei S, Kitaura H, Zhou P et al. (2005) IL-1 mediates TNF-induced osteoclastogenesis. J Clin Invest 115: 282–290

    Article  PubMed  CAS  Google Scholar 

  37. Wong PK, Quinn JM, Sims NA et al. (2006) Interleukin-6 modulates production of T lymphocyte-derived cytokines in antigen-induced arthritis and drives inflammation-induced osteoclastogenesis. Arthritis Rheum 54: 158–168

    Article  PubMed  CAS  Google Scholar 

  38. Yoshida H, Hayashi S, Kunisada T et al. (1990) The murine mutation osteopetrosis is in the coding region of the macrophage colony stimulating factor gene. Nature 345: 442–444

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Abteilung für Innere Medizin und Rheumatologie, Justus-Liebig-Universität, Gießen, Deutschland

    E. Neumann

  2. Medizinische Klinik III und Institut für klinische Immunologie, Friedrich-Alexander-Universität Erlangen-Nürnberg, Krankenhausstraße 12, 91054, Erlangen, Deutschland

    G. Schett

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Neumann, E., Schett, G. Knochenstoffwechsel. Z. Rheumatol. 66, 286–289 (2007). https://doi.org/10.1007/s00393-007-0182-4

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  • DOI: https://doi.org/10.1007/s00393-007-0182-4

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