Background/Purpose: The role of endogenous glucocorticoids (GC) in, and their contribution to the susceptibility and severity of rheumatoid arthritis remains inconclusive. We previously demonstrated that disruption of GC signaling in osteoblasts results in attenuation of arthritis in the antibody-mediated mouse model of K/BxN serum-induced arthritis (Buttgereit et al., Arthritis Rheum 2009). The aim of this study was to test whether GC-dependent osteoblast effects have a similar impact on the T cell-mediated model 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. Arthritis was induced by intra-articular injection of mBSA into one knee joint of pre-immunised 11-week old male transgenic mice (tg) and their wild-type (WT) littermates. Controls received PBS. Knee joint swelling was assessed continuously for 14 days until the mice were sacrificed. The mice were examined by histology, histomorphometry, and micro-CT. In a part of the animals, arthritis was prolonged through three weekly repeated intravenous injections of mBSA until day 28. Statistical analysis was performed by repeated measures analysis.

Results: Acute and significant arthritis developed in both 11β-HSD2-tg and WT mice with maximum knee joint swelling on day 1 and abatement thereafter, with no significant difference in knee joint swelling between tg (n=14) and WT mice (n=17). Histological indices of inflammation, cartilage damage and bone erosion of WT and tg mice, respectively, accordingly showed no differences. Bone turnover and bone volume measured at the contralateral knee remained unchanged. In the prolonged AIA model with repeated intravenous antigen boosts, a significant arthritis with flares on days 7, 14 and 21 was achieved, but also without significant differences between tg mice (n=7) and their WT littermates (n=8) and corroborating histological findings.

Conclusion: In contrast to K/BxN serum-induced arthritis, murine antigen-induced arthritis is resistant to disruption of GC signaling in osteoblasts. This suggests that osteoblasts do not modulate the T cell-mediated inflammatory response but the antibody-mediated inflammatory response (complement, Fc receptors, neutrophils, monocytes/macrophages) via a GC-dependent pathway.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/t-cell-mediated-murine-antigen-induced-arthritis-is-resistant-to-transgenic-disruption-of-glucocorticoid-signaling-in-osteoblasts-and-osteocytes-in-vivo/