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AB0085 Murine antigen-induced arthritis is not affected by transgenic disruption of osteoblastic glucocorticoid signaling
  1. C. M. Spies1,
  2. E. Wiebe1,2,
  3. J. W. Tu2,
  4. T. Gaber1,3,4,
  5. D. Huscher1,4,
  6. M. Seibel2,5,
  7. H. Zhou2,
  8. F. Buttgereit1
  1. 1Department Of Rheumatology And Clinical Immunology, Charité - University Medicine Berlin, Berlin, Germany
  2. 2Bone Research Program, ANZAC Research Institute, The University of Sydney, Sydney, Australia
  3. 3Berlin-Brandenburg Center of Regenerative Therapies (BCRT)
  4. 4German Rheumatism Research Center (DRFZ), Berlin, Germany
  5. 5Department of Endocrinology & Metabolism, Concord Repatriation Hospital, The University of Sydney, Sydney, Australia

Abstract

Background The role of endogenous glucocorticoids (GC) in the initiation and maintenance of rheumatoid arthritis (RA) remains unclear. We demonstrated previously that disruption of GC signaling in osteoblasts results in a profound attenuation of arthritis in the K/BxN serum-induced mouse model of RA (1).

Objectives To determine whether or not the modulation of the inflammatory response by osteoblasts involves T cells, we studied the effects of disrupted osteoblastic GC-signaling in the T cell-dependentmodel of antigen-induced arthritis (AIA).

Methods GC signaling in osteoblasts was disrupted by transgenic overexpression of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) under the control of a type I collagen promoter. Acute arthritis was induced in pre-immunized 11-week-old male transgenic (tg) mice and their wild-type (WT) litter-mates by intra-articular injection of mBSA into one knee joint. Knee diameter was measured every 1-2 days until euthanasia on day 14 post injection. In a separate experiment, arthritis was maintained for 28 days by weekly intravenous reinjections of mBSA. Tissues were analyzed by histology, histomorphometry and microfocal-computed tomography. Serum cytokines levels were determined by multiplex suspension array.

Results In both short and long term experiments, arthritis developed in tg and WT mice with no significant difference between both groups. Histological indices of inflammation, cartilage damage and bone erosion were similar in tg and WT mice. Bone volume and turnover at the contralateral tibia and systemic cytokine levels remained unchanged.

Conclusions In contrast to K/BxN serum-induced arthritis, murine AIA is not affected by a disruption in osteoblastic GC signaling. These data indicate that osteoblasts do not modulate the T cell-mediated, but rather the immune complex-mediated inflammatory response via a GC-dependent pathway.

  1. Buttgereit et al. Arthritis Rheum 2009.

Acknowledgements This work was supported by a grant from the German Research Foundation (DFG) in association with the Priority Program SPP 1468 “Osteoimmunology IMMUNOBONE – A Program to Unravel the Mutual Interactions between the Immune System and Bone” and by the National Health & Medical Research Council, Australia.

Disclosure of Interest None Declared

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