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

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 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).

METHODS:

Acute 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.

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 were not different.

CONCLUSIONS:

Acute 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.

• Authors: Cornelia M Spies, Edgar Wiebe, Jinwen Tu, Aiqing Li, Timo Gaber, Dörte Huscher, Markus J Seibel, Hong Zhou, Frank Buttgereit
• Journal: BMC musculoskeletal disorders (BMC Musculoskelet Disord) Vol. 15 Pg. 31 (Feb 03 2014) ISSN: 1471-2474 [Electronic] England
• PMID: 24491163 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Glucocorticoids
• Inflammation Mediators
• methylated bovine serum albumin
• Serum Albumin, Bovine
• 11-beta-Hydroxysteroid Dehydrogenase Type 2

Topics

• 11-beta-Hydroxysteroid Dehydrogenase Type 2 (genetics, metabolism)
• Animals
• Arthritis, Experimental (chemically induced, diagnosis, enzymology, genetics, immunology, metabolism)
• Cytokines (blood)
• Glucocorticoids (metabolism)
• Inflammation Mediators (blood)
• Knee Joint (diagnostic imaging, enzymology, immunology, metabolism)
• Male
• Mice
• Mice, Transgenic
• Osteoblasts (enzymology, immunology, metabolism)
• Serum Albumin, Bovine
• Signal Transduction
• T-Lymphocytes (immunology, metabolism)
• Time Factors
• X-Ray Microtomography