Drs. Stolina, Zack, Kostenuik, Feige, and Ms Dwyer own stock or stock options in Amgen Inc.
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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
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Abstract
Objective
To investigate the kinetics of bony spur formation and the relationship of bony spur formation to synovial inflammation and bone erosion in 2 rat arthritis models, and to address whether bony spur formation depends on the expression of tumor necrosis factor α (TNFα) or RANKL.
Methods
Analysis of the kinetics of synovial inflammation, bone erosion, osteoclast formation, and growth of bony spurs was performed in rat collagen-induced arthritis (CIA) and adjuvant-induced arthritis (AIA). In addition, inhibition experiments were performed to assess whether inhibition of TNFα and RANKL by pegylated soluble TNF receptor type I (pegTNFRI) and osteoprotegerin (OPG), respectively, affected bony spur formation.
Results
Bony spurs emerged from the periosteal surface close to joints, and initial proliferation of mesenchymal cells was noted as early as 3 days and 5 days after onset of CIA and AIA, respectively. Initiation of bony spur formation occurred shortly after the onset of inflammation and bone erosion. Neither pegTNFRI nor OPG could significantly halt the osteophytic responses in CIA and AIA.
Conclusion
These results suggest that bony spur formation is triggered by inflammation and initial structural damage in these rat models of inflammatory arthritis. Moreover, emergence of bony spurs depends on periosteal proliferation and is not affected by inhibition of either TNFα or RANKL. Bony spur formation can thus be considered a process that occurs independent of TNFα and RANKL and is triggered by destructive arthritis.