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OP0187 Transgenic disruption of glucocorticoid-signaling in mature osteoblasts and osteocytes attenuates structural bone damage in a long-term murine k/bxn serum-induced arthritis model
  1. E Wiebe1,2,
  2. C Spies1,2,
  3. J Tu2,
  4. T Maleitzke1,2,
  5. Y Zhang2,
  6. M Seibel2,3,
  7. H Zhou2,
  8. F Buttgereit4
  1. 1Department of Rheumatology and Clinical Immunology, Charité University Hospital, Berlin, Germany
  2. 2Bone Research Program, ANZAC Research Institute, University of Sydney
  3. 3Department of Endocrinology and Metabolism, Concord Repatriation Hospital, University of Sydney, Sydney, New South Wales, Australia
  4. 4Department of Rheumatology and Clinical Immunology, Charité Universitätsmedizin Berlin, Berlin, Germany


Background The role of endogenous glucocorticoids (GC) in bone metabolism in chronic inflammatory arthritis remains unclear. We have previously shown that disruption of GC-signaling in osteoblasts results in a marked attenuation of arthritis in the K/BxN serum-induced and CAIA mouse model with preservation of bone volume and structure1,2.

Objectives In order to investigate the impact of endogenous GCs on bone erosion and turnover in chronic inflammatory arthritis, we now studied the effects of disrupted osteoblastic GC-signaling in a long-term murine arthritis model.

Methods Intracellular GC-signaling in osteoblasts was disrupted by transgenic overexpression of 11beta-hydroxysteroid dehydrogenase type 2 (11β-HSD type 2) under the control of a type 1 collagen promoter. Arthritis was induced in 5-week old male transgenic (tg) mice and their wild-type (WT) littermates. In order to maintain a chronically active arthritis, mice were boosted on day 14 and 28 by subcutaneous injection of K/BxN serum, controls (CTR) received PBS, respectively. Severity of arthritis was assessed daily by clinical scoring and ankle size measurements until the endpoint (day 42). Ankle joints were assessed by a histopathologic score and microfocal computed tomography (micro-CT). Systemic effects of inflammation on bone metabolism were quantified by histomorphometry and micro-CT of the tibia.

Results Acute Arthritis developed in both tg and WT mice and remained active over the period of 42 days, with a reduced, yet non-significant, severity in tg compared to WT mice. Histological indices of inflammation, cartilage damage and especially bone erosion, additionally assessed by micro-CT, tended to be overall reduced in tg mice, yet not reaching a level of significance. Bone volume and bone turnover did not differ between tg and WT arthritic mice.

Conclusions The modulating effect of disrupted GC-signaling in osteoblasts in serum-induced autoimmune-arthritis prevails in a chronic inflammatory setting, leading to less severe local inflammation and bone destruction. This supports the important role of endogenous GCs for an intact bone metabolism in inflammatory bone disease.


  1. Tu J, Zhang Y, Kim S, Wiebe E, Spies CM, Buttgereit F, et al. Transgenic Disruption of Glucocorticoid Signaling in Osteoblasts Attenuates Joint Inflammation in Collagen Antibody-Induced Arthritis. Am J Pathol. 2016;186(5):1293–301.

  2. Buttgereit F, Zhou H, Kalak R, Gaber T, Spies CM, Huscher D, et al. Transgenic disruption of glucocorticoid signaling in mature osteoblasts and osteocytes attenuates K/BxN mouse serum-induced arthritis in vivo. Arthritis Rheum. 2009;60(7):1998–2007.


Disclosure of Interest None declared

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