Artikel
Structural bone damage in a long-term K/BxN serum-induced arthritis model tends to be attenuated by transgenic disruption of osteoblastic glucocorticoid-signaling
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Autoren
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Edgar Wiebe
- Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, Berlin
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Cornelia Spies
- Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, Berlin
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Jinwen W. Tu
- The University of Sydney, ANZAC Research Institute, Bone Biology Research Program, Sydney, Australia
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Tazio Maleitzke
- Charité Universitätsmedizin Berlin, Berlin
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Yaqing Zhang
- ANZAC Research Institute University of Sydney, Sydney, Australien
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Markus Seibel
- The University of Sydney, ANZAC Research Institute, Bone Biology Research Program, Sydney, Australia
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Hong Zhou
- The University of Sydney, ANZAC Research Institute, Bone Biology Research Program, Sydney, Australia
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Frank Buttgereit
- Charité-Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, Berlin
| Veröffentlicht: | 4. September 2017 |
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Gliederung
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Background: Endogenous glucocorticoids (GC) seem to play an important role in the modulation of immune-mediated inflammatory processes of arthritis. We have previously shown that disruption of GC-signaling in osteoblasts results in a marked attenuation of arthritis in the K/BxN serum-induced as well as the CAIA mouse model with preservation of bone volume and structure. However, the effect of endogenous GCs on bone metabolism in a chronic inflammatory setting remains unclear.
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 K/BxN arthritis model.
Methods: Intracellular GC-signaling in osteoblasts was disrupted by transgenic overexpression of 11beta-hydroxysteroid dehydrogenase type 2 (11ß-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. Clinically, albeit not statistically significant, the severity of arthritis tended to be lower in tg compared to WT mice. Correspondingly, histological indices of inflammation, cartilage damage and especially bone erosion, as corroborated by micro-CT, tended to be reduced in tg mice - yet also not reaching a level of statistical significance. No difference was observed for bone volume and turnover.
Conclusion: The modulating effect of disrupted GC-signaling in osteoblasts in serum-induced autoimmune-arthritis seems to prevail also in a chronic inflammatory setting with attenuated local inflammation and bone destruction. This supports the potentially important role of endogenous GCs for an intact bone metabolism in inflammatory bone disease.
