Acute murine antigen-induced arthritis is not affected by disruption of osteoblastic glucocorticoid signalling

Abstract

BackgroundThe role of endogenous glucocorticoids (GC) in the initiation and maintenance of rheumatoid arthritis (RA) remains unclear. We demonstrated previously that disruption of GC signalling in osteoblasts results in a profound attenuation of K/BxN serum-induced arthritis, a mouse model of RA. To determine whether or not the modulation of the inflammatory response by osteoblasts involves T cells, we studied the effects of disrupted osteoblastic GC-signalling in the T cell-dependent model of antigen-induced arthritis (AIA).MethodsAcute arthritis was induced in pre-immunised 11-week-old male 11β-hydroxysteroid dehydrogenase type 2 transgenic (tg) mice and their wild-type (WT) littermates by intra-articular injection of methylated bovine serum albumine (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 reinjections of mBSA. Tissues were analysed by histology, histomorphometry and microfocal-computed tomography. Serum cytokines levels were determined by multiplex suspension array.ResultsIn 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 were not different.ConclusionsAcute murine AIA is not affected by a disruption in osteoblastic GC signalling. These data indicate that osteoblasts do not modulate the T cell-mediated inflammatory response via a GC-dependent pathway.

Endogenous glucocorticoid signaling in chondrocytes attenuates joint inflammation and damage

“…Interestingly, disruption of endogenous glucocorticoid signaling in chondrocytes appears to have the opposite effect on inflammatory arthritis compared to that mediated by osteoblasts. In addition, our previous study showed that murine AIA is not affected by disruption of glucocorticoid signaling in osteoblasts (8), while in the current study, chondrocytes appear to regulate inflammation in the AIA model through endogenous glucocorticoid signaling. The differential modulations of immune arthritis by osteoblasts and chondrocytes can be due to the distinct soluble factors secreted by these 2 cell types.…”

“…AIA was initiated in both WT and chGRKO mice as previously described (8,12). Eight-week-old chGRKO mice and their WT littermates were immunized by subcutaneous injection of 100 mg methylated bovine serum albumin (mBSA; Sigma-Aldrich) dissolved in 50 ml PBS and emulsified in 50 ml Freund complete adjuvant (Sigma-Aldrich) into both flanks (50 mg each) on d 21.…”

“…We have previously demonstrated in mice that osteoblasts control the severity of inflammatory arthritis via a mechanism dependent on endogenous glucocorticoid signaling. Interestingly, however, while this effect was observed in both K/BxN serum transfer-induced arthritis (STIA) (6) and collagen antibody-induced arthritis models (7), endogenous GC signaling appeared to have no effect on inflammatory activity in the antigen-induced arthritis (AIA) model (8).…”

Secondary osteoporosis in collagen-induced arthritis rats

“…The regions of interest of femoral cancellous bone were chosen for analysis. With use of the cross-sectional images from micro-CT scanning, longitudinal analysis of the distal femur excluding the cortical bone was performed in the measurement area between 1 and 4 mm distal to the growth plate-metaphysis junction [10,18]. Bone volume/total volume (BV/TV), structure model index (SMI), trabecular number (Tb.N), trabecular separation (Tb.Sp), trabecular thickness (Tb.Th), and connectivity density (Conn.D) at the left distal femur were measured.…”

Mouse Osteoblasts Play a Crucial Role in the Immune System

“…In 2014, the same group reported that acute murine antigeneinduced arthritis, a T-celledependent arthritis model, is not affected by disruption of osteoblastic endogenous GC signaling. 9 These data indicate that osteoblasts do not modulate the T-cellemediated response via an endogenous GC-dependent pathway.…”