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BMC Musculoskeletal Disorders

, 15:31

Pathophysiology of musculoskeletal disorders

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.

Keywords11-beta-hydroxysteroid dehydrogenase type 2 Disease models Animal Arthritis Glucocorticoids Osteoblasts AbbreviationsAIAAntigen-induced arthritis

basic-FGFBasic fibroblast growth factor

BV-TVBone volume-tissue volume

CFAFreund’s complete adjuvant

Col2.32.3-kb collagen type Iα1 promotor

CTRControls

EDTAEthylenediaminetetraacetic acid

GCGlucocorticoids

G-CSFGranulocyte colony-stimulating factor

GM-CSFGranulocyte macrophage colony-stimulating factor

HandEHaematoxylin and eosin

11β-HSD211β-hydroxysteroid dehydrogenase type 2

ILInterleukin

IFN-γInterferon-γ

KCKeratinocyte-derived cytokine

LIFLeukaemia inhibitory factor

M-CSFMacrophage colony-stimulating factor

mBSAMethylated bovine serum albumine

MCP-1Monocyte chemotactic protein-1

micro-CTMicrofocal-computed tomography

MIFMacrophage migration inhibitory factor

MIGMonokine-induced by interferon-gamma

MIP-1αMacrophage inflammatory protein 1α

MMPMatrix metalloproteinases

N.Oc-BSOsteoclast number-bone surface

Ob.S-BSOsteoblast surface-bone surface

Oc.S-BSOsteoclast surface-bone surface

PBSPhosphate-buffered saline

PDGF-BBPlatelet-derived growth factor homodimer

RARheumatoid arthritis

RANKLReceptor activator of nuclear factor kappa-B ligand

RANTESRegulated upon activation normal T cell expressed and secreted

SDStandard deviation

SEMStandard error of the mean

Tb.NTrabecular number

Tb.SpTrabecular separation

Tb.ThTrabecular thickness

tgTransgenic

TRAPTartrate-resistant acid phosphatase

TNF-αTumour necrosis factor α

u-PAUrokinase-type plasminogen activator

VEGFVascular endothelial growth factor

WTWild-type.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2474-15-31 contains supplementary material, which is available to authorized users.

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Autor: Cornelia M Spies - Edgar Wiebe - Jinwen Tu - Aiqing Li - Timo Gaber - Dörte Huscher - Markus J Seibel - Hong Zhou - Fra

Fuente: https://link.springer.com/



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