Current Rheumatology Reports

, Volume 10, Issue 4, pp 311–317 | Cite as

Altered bone remodeling in psoriatic arthritis

  • Kofi A. Mensah
  • Edward M. SchwarzEmail author
  • Christopher T. Ritchlin


Bone is a highly dynamic organ that interacts with a wide array of cells and tissues. Recent studies have unveiled unanticipated connections between the immune and skeletal systems, and this relationship led to the development of a new field called osteoimmunology. This field will enable investigators to translate basic science findings in bone biology to clinical applications for inflammatory joint diseases such as psoriatic arthritis (PsA). This review examines the disruption of bone homeostasis in PsA and discusses the pivotal role of osteoclasts, osteoblasts, and signaling pathways in the altered remodeling observed in this inflammatory arthritis. It also discusses the effects of tumor necrosis factor inhibition on bone resorption and new bone formation in PsA.


Bone Formation Psoriatic Arthritis Tumor Necrosis Factor Inhibition Osteoclast Precursor Tumor Necrosis Factor Gene 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References and Recommended Reading

  1. 1.
    Teitelbaum SL: Osteoclasts: what do they do and how do they do it? Am J Pathol 2007, 170: 427–435.PubMedCrossRefGoogle Scholar
  2. 2.
    Rho J, Takami M, Choi Y: Osteoimmunology: interactions of the immune and skeletal systems. Mol Cells 2004, 17: 1–9.PubMedGoogle Scholar
  3. 3.
    Rodan GA, Martin TJ: Therapeutic approaches to bone disease. Science 2000, 289: 1508–1514.PubMedCrossRefGoogle Scholar
  4. 4.
    Takayanagi H, Ogasawara K, Hida S, et al.: T-cell-mediated regulation of osteoclastogenesis by signaling crosstalk between RANKL and IFN-gamma. Nature 2000, 408: 600–605.PubMedCrossRefGoogle Scholar
  5. 5.
    Boyle WJ, Simonet WS, Lacey DL: Osteoclast differentiation and activation. Nature 2003, 423: 337–342.PubMedCrossRefGoogle Scholar
  6. 6.
    Lories RJ, Derese I, Luyten FP: Modulation of bone morphogenetic protein signaling inhibits the onset and progression of ankylosing enthesitis. J Clin Invest 2005, 115: 1571–1579.PubMedCrossRefGoogle Scholar
  7. 7.
    Walsh MC, Kim N, Kadono Y, et al.: Osteoimmunology: interplay between the immune system and bone metabolism. Annu Rev Immunol 2006, 24: 33–63.PubMedCrossRefGoogle Scholar
  8. 8.
    Takayanagi H: Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems. Nat Rev Immunol 2007, 7: 292–304.PubMedCrossRefGoogle Scholar
  9. 9.
    Baron R, Rawadi G: Minireview: Targeting the Wnt/B-Catenin pathway to regulate bone formation in the adult skeleton. Endocrinology 2007, 148: 2635–2643.PubMedCrossRefGoogle Scholar
  10. 10.
    Yamaguchi A, Komori T, Suda T: Reulation of osteoblast differentiation mediated by bone morphogenetic proteins, hedgehogs and Cbfa1. Endocrine Reviews 2000, 21: 393–411.PubMedCrossRefGoogle Scholar
  11. 11.
    Diarra D, Stolina M, Polzer K, et al.: Dickkopf-1 is a master regulator of joint remodeling. Nat Medicine 2007, 13: 156–163.CrossRefGoogle Scholar
  12. 12.
    Miyamoto T, Ohneda O, Arai F, et al.: Bifurcation of osteoclasts and dendritic cells from common progenitors. Blood 2001, 98: 2544–2554.PubMedCrossRefGoogle Scholar
  13. 13.
    Arai F, Miyamoto T, Ohneda O, et al.: Commitment and differentiation of osteoclast precursor cells by the sequential expression of c-Fms and receptor activator of nuclear factor {kappa}B (RANK) receptors. J Exp Med 1999, 190: 1741–1754.PubMedCrossRefGoogle Scholar
  14. 14.
    Vignery A: Macrophage fusion: the making of osteoclasts and giant cells. J Exp Med 2005, 202: 337–340.PubMedCrossRefGoogle Scholar
  15. 15.
    Kukita T, Wada N, Kukita A, et al.: RANKL-induced DC-STAMP is essential for osteoclastogenesis. J Exp Med 2004, 200: 941–946.PubMedCrossRefGoogle Scholar
  16. 16.
    Yagi M, Miyamoto T, Sawatani Y, et al.: DC-STAMP is essential for cell-cell fusion in osteoclasts and foreign body giant cells. J Exp Med 2005, 202: 345–351.PubMedCrossRefGoogle Scholar
  17. 17.
    Roodman GD: Advances in bone biology, the osteoclast. Endocr Rev 1996, 17: 308–332.PubMedCrossRefGoogle Scholar
  18. 18.
    Teitelbaum SL: Bone resorption by osteoclasts. Science 2000, 289: 1504–1508.PubMedCrossRefGoogle Scholar
  19. 19.
    Wong BR, Rho J, Arron J, et al.: 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 1997, 272: 25190–25194.PubMedCrossRefGoogle Scholar
  20. 20.
    Anderson DM, Maraskovsky E, Billingsley WL, et al.: A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function. Nature 1997, 390: 175–179.PubMedCrossRefGoogle Scholar
  21. 21.
    Kong YY, Feige U, Sarosi I, et al.: Activated T-cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand. Nature 1999, 402: 304–309.PubMedCrossRefGoogle Scholar
  22. 22.
    Kim N, Odgren PR, Kim DK, et al.: 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: 10905–10910.PubMedCrossRefGoogle Scholar
  23. 23.
    Fitzgerald O: Advances in understanding and novel therapeutic targets in inflammatory arthritis. Ir J Med Sci 1995, 164: 4–11.PubMedCrossRefGoogle Scholar
  24. 24.
    Ritchlin C, Haas-Smith SA, Hicks D, et al.: Patterns of cytokine production in psoriatic synovium. J Rheumatol 1998, 25: 1544–1552.PubMedGoogle Scholar
  25. 25.
    Partsch G, Steiner G, Leeb BF, et al.: Highly increased levels of tumor necrosis factor-a and other proinflammatory cytokines in psoriatic arthritis synovial fluid. J Rheumatol 1997, 24: 518–523.PubMedGoogle Scholar
  26. 26.
    McInnes IB, Illei GG, Danning CL: IL-10 Improves skin disease and modulates endothelial activation and leukocyte effector function in patients with psoriatic arthritis. J Immunol 2001, 167: 4075–4082.PubMedGoogle Scholar
  27. 27.
    Gladman DD, Farewell VT, Nadeau C, et al.: Clinical indicators of progression in psoriatic arthritis: multivariate relative risk model. J Rheumatol 1995, 22: 675–679.PubMedGoogle Scholar
  28. 28.
    Suda T, Takahashi N, Udagawa N, et al.: Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families. Endocr Rev 1999, 20: 345–357.PubMedCrossRefGoogle Scholar
  29. 29.
    Li P, Schwarz EM: The TNF-alpha transgenic mouse model of inflammatory arthritis. Springer Semin Immunopathol 2003, 25: 19–33.PubMedCrossRefGoogle Scholar
  30. 30.
    Abu-Amer Y, Erdmann J, Kollias G, et al.: Tumor necrosis factor receptors types 1 and 2 differentially regulate osteoclastogenesis. J Biol Chem 2000, 275: 27307–27310.PubMedGoogle Scholar
  31. 31.
    Keffer J, Probert L, Cazlaris H, et al.: Transgenic mice expressing human tumour necrosis factor: a predictive genetic model of arthritis. EMBO J 1991, 10: 4025–4031.PubMedGoogle Scholar
  32. 32.
    Li P, Schwarz EM, O’Keefe RJ, et al.: Systemic tumor necrosis factor alpha mediates an increase in peripheral CD11bhigh osteoclast precursors in tumor necrosis factor alpha-transgenic mice. Arthritis Rheum 2004, 50: 265–276.PubMedCrossRefGoogle Scholar
  33. 33.
    Zenz R, Eferl R, Kenner L, et al.: Psoriasis-like skin disease and arthritis caused by inducible epidermal deletion of Jun proteins. 2005, 437: 369–375.Google Scholar
  34. 34.
    Simonet WS, Lacey DL, Dunstan CR, et al.: Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 1997, 89: 309–319.PubMedCrossRefGoogle Scholar
  35. 35.
    Mease PJ: Tumor necrosis factor (TNF) in psoriatic arthritis: pathophysiology and treatment with TNF inhibitors. Ann Rheum Dis 2002, 61: 298–304.PubMedCrossRefGoogle Scholar
  36. 36.
    Rahman P, Siannis F, Butt C, et al.: TNFa polymorphisms and risk of psoriatic arthritis. Ann Rheum Dis 2006, 65: 919–923.PubMedCrossRefGoogle Scholar
  37. 37.
    Ritchlin CT, Haas-Smith S, Li P, et al.: Mechanisms of TNF-a-and RANKL-mediated osteoclastogenesis and bone resorption in psoriatic arthritis. J Clin Invest 2003, 111: 821–831.PubMedGoogle Scholar
  38. 38.
    Anandarajah AP, Schwarz EM, Totterman S, et al.: The effect of etanercept on osteoclast precursor frequency and enhancing bone marrow oedema in patients with psoriatic arthritis. Ann Rheum Dis 2008, 67: 296–301.PubMedCrossRefGoogle Scholar
  39. 39.
    Kaneki H, Guo R, Chen D, et al.: Tumor necrosis factor promotes runx2 degradation through up-regulation of smurf1 and smurf2 in osteoblasts. J Biol Chem 2006, 281: 4326–4333.PubMedCrossRefGoogle Scholar
  40. 40.
    Mease PJ: Psoriatic arthritis update. Bull NYU Hosp Jt Dis 2006, 64: 25–31.PubMedGoogle Scholar
  41. 41.
    van der Heijde D, Kavanaugh A, Gladman DD, et al.: Infliximab inhibits progression of radiographic damage in patients with active psoriatic arthritis through one year of treatment: Results from the induction and maintenance psoriatic arthritis clinical trial 2. Arthritis Rheum 2007, 56: 2698–2707.PubMedCrossRefGoogle Scholar
  42. 42.
    Mease PJ, Gladman DD, Ritchlin CT, et al.; Adalimumab Effectiveness in Psoriatic Arthritis Trial Study Group: Adalimumab for the treatment of patients with moderately to severely active psoriatic arthritis: results of a double-blind, randomized, placebo-controlled trial. Arthritis Rheum 2005, 52: 3279–3289.PubMedCrossRefGoogle Scholar
  43. 43.
    Van der Heijde DM, Landewe RD, Ory P, et al.: Etanercept does not inhibit radiographic progression in patients with ankylosing spondylitis [abstract]. Ann Rheum Dis 2006, 65(SII): 81.Google Scholar
  44. 44.
    Lories RJ, Derese I, Bari C, et al.: Evidence for uncoupling of inflammation and joint remodeling in a mouse model of spondylarthritis. Arthritis Rheum 2007, 56: 489–497.PubMedCrossRefGoogle Scholar
  45. 45.
    Taylor W, Gladman D, Helliwell P, et al.: Classification criteria for psoriatic arthritis: development of new criteria from a large international study. Arthritis Rheum 2006, 54: 2665–2673.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Kofi A. Mensah
  • Edward M. Schwarz
    • 1
    Email author
  • Christopher T. Ritchlin
  1. 1.Department of OrthopaedicsUniversity of Rochester Medical CenterRochesterUSA

Personalised recommendations