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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
  1. E Lubberts1,
  2. L Joosten1,
  3. P Schwarzenberger2,
  4. B Oppers1,
  5. L Van den Bersselaar1,
  6. JK Kolls2,
  7. WB Van den Berg1
  1. 1Rheumatology Research Lab., University Medical Center St Radboud, Nijmegen, The Netherlands
  2. 2Gene Therapy Program, Louisiana State University, New Orleans, USA

Abstract

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.

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