Drs. Stolina, Zack, Kostenuik, Feige, and Ms Dwyer own stock or stock options in Amgen Inc.
Experimental Arthritis
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Tumor necrosis factor α and RANKL blockade cannot halt bony spur formation in experimental inflammatory arthritis
Article first published online: 27 AUG 2009
DOI: 10.1002/art.24767
Copyright © 2009 by the American College of Rheumatology
Additional Information
How to Cite
Schett, G., Stolina, M., Dwyer, D., Zack, D., Uderhardt, S., Krönke, G., Kostenuik, P. and Feige, U. (2009), Tumor necrosis factor α and RANKL blockade cannot halt bony spur formation in experimental inflammatory arthritis. Arthritis & Rheumatism, 60: 2644–2654. doi: 10.1002/art.24767
Publication History
- Issue published online: 27 AUG 2009
- Article first published online: 27 AUG 2009
- Manuscript Accepted: 26 MAY 2009
- Manuscript Received: 15 OCT 2008
Funded by
- Sonderforschungsbereich. Grant Number: SBF) 643
- Interdisziplinäres Zentrum für Klinische Forschung Erlangen
- Forschergruppe 661 of the Deutsche Forschungsgemeinschaft (DFG)
- Austrian Ministry of Sciences (START Program award)
- SPIRAL consortium, and the EU projects Masterswitch, Kinacept
- Adipoa
REFERENCES
- 1. Evolving concepts of rheumatoid arthritis. Nature 2003; 423: 356–61.
- 2, . Cytokines in the pathogenesis of rheumatoid arthritis. Nat Immunol 2007; 7: 429–42.
- 3, . Eating bone or adding it: the Wnt pathway decides. Nat Med 2007; 13: 133–4.
- 4, , . TNF blockers and structural remodeling in ankylosing spondylitis—what is reality and what is fiction? Ann Rheum Dis 2007; 66: 709–11.
- 5, , , , , . TNF-α induces osteoclastogenesis by direct stimulation of macrophages exposed to permissive levels of RANK ligand. J Clin Invest 2000; 106: 1481–8.
- 6, , , , , , et al. Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand. Nature 1999; 402: 304–9.
- 7, , , , , , et al. Osteoclasts are essential for TNF-α-mediated joint destruction. J Clin Invest 2002; 110: 1419–27.
- 8, , , , , . Differential modulation of RANKL isoforms by human osteoarthritic subchondral bone osteoblasts: influence of osteotropic factors. Bone 2008; 43: 284–91.
- 9, , , , , , et al. Receptor activator NF-κB ligand (RANKL) expression in synovial tissue from patients with rheumatoid arthritis, spondyloarthropathy, osteoarthritis, and from normal patients: semiquantitative and quantitative analysis. Ann Rheum Dis 2002; 61: 1047–54.
- 10, , . OPG and RANKL regulation of bone remodeling in health and disease. Endocr Rev 2008; 29: 155–92.
- 11, , , , , , et al. Receptor activator of nuclear factor κB ligand (RANKL)/osteoprotegerin (OPG) ratio is increased in severe osteolysis. Am J Pathol 2003; 163: 2021–31.
- 12, , , , , , et al. Osteoprotegerin expression in synovial tissue from patients with rheumatoid arthritis, spondyloarthropathies and osteoarthritis and normal controls. Rheumatology (Oxford) 2003; 42: 123–34.
- 13, , , , , . Identification of cell types responsible for bone resorption in rheumatoid arthritis and juvenile rheumatoid arthritis. Am J Pathol 1998; 152: 943–51.
- 14, , , , , , et al. Tumor necrosis factor α induces expression of genes for matrix degradation in human chondrocyte-like HCS-2/8 cells through activation of NF-κB: abrogation of the tumor necrosis factor α effect by proteosome inhibitors. J Bone Miner Res 2001; 16: 1272–80.Direct Link:
- 15, , , , , , et al. Cytokine production by synovial T cells in rheumatoid arthritis. Rheumatology (Oxford) 1999; 38: 202–13.
- 16, , , , , , et al. Increased levels of soluble tumor necrosis factor receptors in the sera and synovial fluid of patients with rheumatic diseases. Arthritis Rheum 1992; 35: 1160–9.Direct Link:
- 17, . Therapeutic strategies for rheumatoid arthritis. Nat Rev Drug Discov 2003; 2: 473–88.
- 18. The enthesopathy of ankylosing spondylitis. Br J Rheumatol 1983; 22(4 Suppl 2 ): 25–8.
- 19, , , . Critical appraisal of assessment of structural damage in ankylosing spondylitis: implications for treatment outcomes [review]. Arthritis Rheum 2008; 58: 649–56.Direct Link:
- 20, , . Modulation of bone morphogenetic protein signaling inhibits the onset and progression of ankylosing enthesitis. J Clin Invest 2005; 115: 1571–9.
- 21, , , . Reduction of osteophyte formation and synovial thickening by adenoviral overexpression of transforming growth factor β/bone morphogenetic protein inhibitors during experimental osteoarthritis. Arthritis Rheum 2003; 48: 3442–51.Direct Link:
- 22, , , , , , et al. Dickkopf-1 is a master regulator of joint remodeling. Nat Med 2007; 13: 156–63.
- 23, , , , , . Radiological outcome in ankylosing spondylitis: use of the Stoke Ankylosing Spondylitis Spine Score (SASSS). Br J Rheumatol 1996; 35: 373–6.
- 24, , , , , . Assessment of outcome in ankylosing spondylitis: an extended radiographic scoring system. Ann Rheum Dis 2005; 64: 127–9.
- 25, , , , , , et al. Radiographic progression of ankylosing spondylitis after up to two years of treatment with etanercept. Arthritis Rheum 2008; 58: 1324–31.Direct Link:
- 26, , , . Evidence for uncoupling of inflammation and joint remodeling in a mouse model of spondylarthritis. Arthritis Rheum 2007; 56: 489–97.Direct Link:
- 27, , , , , . Anti-interleukin-1 and anti-tumor necrosis factor-α synergistically inhibit adjuvant arthritis in Lewis rats. Cell Mol Life Sci 2000; 57: 1457–70.
- 28, , , , . Osteoclast numbers in Lewis rats with adjuvant-induced arthritis: identification of preferred sites and parameters for rapid quantitative analysis. Vet Pathol 2004; 41: 30–6.
- 29, , , , , , et al. Characterization of human type X procollagen and its NC-1 domain expressed as recombinant proteins in HEK293 cells. J Biol Chem 1998; 273: 4547–55.
- 30, , . Kinetics of bone protection by recombinant osteoprotegerin therapy in Lewis rats with adjuvant arthritis. Arthritis Rheum 2002; 46: 1926–36.Direct Link:
- 31, , , , , , et al. Analysis of the kinetics of osteoclastogenesis in arthritic rats. Arthritis Rheum 2005; 52: 3192–201.Direct Link:
- 32, , , , , , et al. Additive bone-protective effects of anabolic treatment when used in conjuction with RANKL and tumor necrosis factor inhibition in two rat arthritis models. Arthritis Rheum 2005; 52: 1604–11.Direct Link:
- 33
- 34, , , , . Bisphosphonates suppress periosteal osteoblast activity independently of resorption in rat femur and tibia. Bone 2006; 39: 1053–8.
- 35, , , . Growth factor regulation of fracture repair. J Bone Miner Res 1999; 14: 1805–15.Direct Link:
- 36, , , , , , et al. Stromal cell–derived factor 1/CXCR4 signaling is critical for the recruitment of mesenchymal stem cells to the fracture site during skeletal repair in a mouse model. Arthritis Rheum 2009; 60: 813–23.Direct Link:
- 37, , . Effects of long-term estrogen replacement therapy on bone turnover in periarticular tibial osteophytes in surgically postmenopausal cynomolgus monkeys. Bone 2008; 42: 907–13.
- 38, , , , , , et al. Effects of receptor activator of NFκB (RANK) signaling blockade on fracture healing. J Orthop Res 2003; 21: 676–84.Direct Link:
- 39, , , , . Optimal timing of a single dose of zoledronic acid to increase strength in rat fracture repair. J Bone Miner Res 2007; 22: 867–76.Direct Link:
- 40, . Osteoprotegerin treatment impairs remodeling and apparent material properties of callus tissue without influencing structural fracture strength. Calcif Tissue Int 2005; 76: 280–6.
- 41, , , , , , et al. Transgenic mice expressing human tumour necrosis factor: a predictive genetic model of arthritis. EMBO J 1991; 10: 4025–31.
- 42, , , , . Ankylosing enthesitis, dactylitis, and onychoperiostitis in male DBA/1 mice: a model of psoriatic arthritis. Ann Rheum Dis 2004; 63: 595–8.
- 43, . Impact of NSAIDS on murine antigen induced arthritis. II. A light microscopic investigation of antiinflammatory and bone protective effects. J Rheumatol 1990; 17: 295–303.
- 44, , , , . Stimulation of bone resorption and inhibition of bone formation in vitro by human tumor necrosis factor. Nature 1986; 319: 516–8.
- 45. Effects of tumor necrosis factor on bone formation in vitro. Endocrinology 1987; 121: 1596–604.
- 46, , . Inhibition of osteoclasts does not prevent joint ankylosis in a mouse model of spondyloarthritis. Rheumatology (Oxford) 2008; 47: 605–8.
- 47, , , , , , et al, for the Health, Aging and Body Composition Study. The relationship of antiresorptive drug use to structural findings and symptoms of knee osteoarthritis. Arthritis Rheum 2004; 50: 3516–25.Direct Link:
- 48, , , , , , et al, for the AMG 162 Bone Loss Study Group. Denosumab in postmenopausal women with low bone mineral density. N Engl J Med 2006; 354: 821–31.
- 49, , , , , , et al. Impact of degenerative spinal diseases on bone mineral density of the lumbar spine in elderly women. Osteoporos Int 2004; 15: 724–8.

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