Abstract
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.
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References and Recommended Reading
Teitelbaum SL: Osteoclasts: what do they do and how do they do it? Am J Pathol 2007, 170: 427–435.
Rho J, Takami M, Choi Y: Osteoimmunology: interactions of the immune and skeletal systems. Mol Cells 2004, 17: 1–9.
Rodan GA, Martin TJ: Therapeutic approaches to bone disease. Science 2000, 289: 1508–1514.
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.
Boyle WJ, Simonet WS, Lacey DL: Osteoclast differentiation and activation. Nature 2003, 423: 337–342.
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.
Walsh MC, Kim N, Kadono Y, et al.: Osteoimmunology: interplay between the immune system and bone metabolism. Annu Rev Immunol 2006, 24: 33–63.
Takayanagi H: Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems. Nat Rev Immunol 2007, 7: 292–304.
Baron R, Rawadi G: Minireview: Targeting the Wnt/B-Catenin pathway to regulate bone formation in the adult skeleton. Endocrinology 2007, 148: 2635–2643.
Yamaguchi A, Komori T, Suda T: Reulation of osteoblast differentiation mediated by bone morphogenetic proteins, hedgehogs and Cbfa1. Endocrine Reviews 2000, 21: 393–411.
Diarra D, Stolina M, Polzer K, et al.: Dickkopf-1 is a master regulator of joint remodeling. Nat Medicine 2007, 13: 156–163.
Miyamoto T, Ohneda O, Arai F, et al.: Bifurcation of osteoclasts and dendritic cells from common progenitors. Blood 2001, 98: 2544–2554.
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.
Vignery A: Macrophage fusion: the making of osteoclasts and giant cells. J Exp Med 2005, 202: 337–340.
Kukita T, Wada N, Kukita A, et al.: RANKL-induced DC-STAMP is essential for osteoclastogenesis. J Exp Med 2004, 200: 941–946.
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.
Roodman GD: Advances in bone biology, the osteoclast. Endocr Rev 1996, 17: 308–332.
Teitelbaum SL: Bone resorption by osteoclasts. Science 2000, 289: 1504–1508.
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.
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.
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.
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.
Fitzgerald O: Advances in understanding and novel therapeutic targets in inflammatory arthritis. Ir J Med Sci 1995, 164: 4–11.
Ritchlin C, Haas-Smith SA, Hicks D, et al.: Patterns of cytokine production in psoriatic synovium. J Rheumatol 1998, 25: 1544–1552.
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.
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.
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.
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.
Li P, Schwarz EM: The TNF-alpha transgenic mouse model of inflammatory arthritis. Springer Semin Immunopathol 2003, 25: 19–33.
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.
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.
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.
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.
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.
Mease PJ: Tumor necrosis factor (TNF) in psoriatic arthritis: pathophysiology and treatment with TNF inhibitors. Ann Rheum Dis 2002, 61: 298–304.
Rahman P, Siannis F, Butt C, et al.: TNFa polymorphisms and risk of psoriatic arthritis. Ann Rheum Dis 2006, 65: 919–923.
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.
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.
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.
Mease PJ: Psoriatic arthritis update. Bull NYU Hosp Jt Dis 2006, 64: 25–31.
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.
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.
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.
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.
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.
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Mensah, K.A., Schwarz, E.M. & Ritchlin, C.T. Altered bone remodeling in psoriatic arthritis. Curr Rheumatol Rep 10, 311–317 (2008). https://doi.org/10.1007/s11926-008-0050-5
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DOI: https://doi.org/10.1007/s11926-008-0050-5