THU0039 Local il-17 gene therapy accelerates collagen arthritis with severe bone erosion and rank ligand and rank expression in synovial infiltrate and at bone erosion sites. (1st June 2001)

• Record Type: Journal Article
• Authors: Lubberts, E; Joosten, L; Schwarzenberger, P; Oppers, B; Van den Bersselaar, L; Kolls, JK; Van den Berg, WB
• Is Part Of: Annals of the rheumatic diseases. Volume 60(2001)Supplement 1
• Page Start: A328
• Page End: A328
• Publication Date: 2001-06-01
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2001.836
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Background: Objectives: To examine the effects of local IL-17 application in the knee joint of type II collagen immunised mice on the induction of bone erosion. Methods: Collagen induced arthritis (CIA) was induced in male DBA-1 mice by immunising intradermally at the base of the tail with suboptimal dose of bovine type II collagen. On day 21, mice were given a booster injection (i.p.) of the same dose of type II dissolved in PBS. Just before expected onset, mice were intraarticularly (i.a.) injected into the right knee joint with 10^7 pfu of either an IL-17 expressing (AdIL-17) or control (AdControl) recombinant human type 5 adenovirus vector. Five days after the i.a. injection of the viral vector, arthritis was monitored visually and joint pathology was examined by histology. Formation of osteoclast-like cells was determined by tartrate-resistant acid phosphatase (TRAP) staining. In addition, RANKL and RANK protein expression was evaluated by specific immunohistochemistry. Results: Local IL-17 over-expression in the knee joint of type II collagen immunised mice promotes synovial inflammation. Five days after viral injection of AdIL-17, histologic analysis showed aggravation of bone erosion in the patella and femur/tibia region compared with the control vector group. Induction of bone destruction by IL-17 was accompanied with marked TRAP activity in the bone marrow and at bone erosion sites, indicating that IL-17 accelerates the formation of osteoclast-like cells. Interestingly, local IL-17 promotes local protein expression of RANKL and its receptor RANK in the synovial infiltrate and at bone erosion sites compared with the control vector group. Conclusion: These data shows that local IL-17 gene therapy during onset of collagen arthritis promotes osteoclastic bone erosion accompanied with accelerated expression of local RANKL and its receptor RANK. These findings suggest IL-17 to be a potent stimulator of osteoclastogenesis during arthritis.