TY - JOUR

T1 - Kinetics of gene expression and bone remodelling in the clinical phase of collagen induced arthritis

AU - Denninger, Katja Caroline Marie

AU - Litman, Thomas

AU - Marstrand, Troels

AU - Moller, Kristian

AU - Svensson, Lars

AU - Labuda, Tord

AU - Andersson, Åsa

PY - 2015

Y1 - 2015

N2 - Introduction: Pathological bone changes differ considerably between inflammatory arthritic diseases and moststudies have focused on bone erosion. Collagen-induced arthritis (CIA) is a model for rheumatoid arthritis, which,in addition to bone erosion, demonstrates bone formation at the time of clinical manifestations. The objective ofthis study was to use this model to characterise the histological and molecular changes in bone remodelling, andrelate these to the clinical disease development.Methods: A histological and gene expression profiling time-course study on bone remodelling in CIA was linked toonset of clinical symptoms. Global gene expression was studied with a gene chip array system.Results: The main histopathological changes in bone structure and inflammation occurred during the first twoweeks following the onset of clinical symptoms in the joint. Hereafter, the inflammation declined and remodellingof formed bone dominated.Global gene expression profiling showed simultaneous upregulation of genes related to bone changes andinflammation in week 0 to 2 after onset of clinical disease. Furthermore, we observed time-dependent expression ofgenes involved in early and late osteoblast differentiation and function, which mirrored the histopathological bonechanges. The differentially expressed genes belong to the bone morphogenetic pathway (BMP) and, in addition,include the osteoblast markers integrin-binding sialoprotein (Ibsp), bone gamma-carboxyglutamate protein (Bglap1),and secreted phosphoprotein 1 (Spp1). Pregnancy-associated protein A (Pappa) and periostin (Postn), differentiallyexpressed in the early disease phase, are proposed to participate in bone formation, and we suggest that they playa role in early bone formation in the CIA model. Comparison to human genome-wide association studies (GWAS)revealed differential expression of several genes associated with human arthritis.Conclusions: In the CIA model, bone formation in the joint starts shortly after onset of clinical symptoms, whichresults in bony fusion within one to two weeks. This makes it a candidate model for investigating the relationshipbetween inflammation and bone formation in inflammatory arthritis.

AB - Introduction: Pathological bone changes differ considerably between inflammatory arthritic diseases and moststudies have focused on bone erosion. Collagen-induced arthritis (CIA) is a model for rheumatoid arthritis, which,in addition to bone erosion, demonstrates bone formation at the time of clinical manifestations. The objective ofthis study was to use this model to characterise the histological and molecular changes in bone remodelling, andrelate these to the clinical disease development.Methods: A histological and gene expression profiling time-course study on bone remodelling in CIA was linked toonset of clinical symptoms. Global gene expression was studied with a gene chip array system.Results: The main histopathological changes in bone structure and inflammation occurred during the first twoweeks following the onset of clinical symptoms in the joint. Hereafter, the inflammation declined and remodellingof formed bone dominated.Global gene expression profiling showed simultaneous upregulation of genes related to bone changes andinflammation in week 0 to 2 after onset of clinical disease. Furthermore, we observed time-dependent expression ofgenes involved in early and late osteoblast differentiation and function, which mirrored the histopathological bonechanges. The differentially expressed genes belong to the bone morphogenetic pathway (BMP) and, in addition,include the osteoblast markers integrin-binding sialoprotein (Ibsp), bone gamma-carboxyglutamate protein (Bglap1),and secreted phosphoprotein 1 (Spp1). Pregnancy-associated protein A (Pappa) and periostin (Postn), differentiallyexpressed in the early disease phase, are proposed to participate in bone formation, and we suggest that they playa role in early bone formation in the CIA model. Comparison to human genome-wide association studies (GWAS)revealed differential expression of several genes associated with human arthritis.Conclusions: In the CIA model, bone formation in the joint starts shortly after onset of clinical symptoms, whichresults in bony fusion within one to two weeks. This makes it a candidate model for investigating the relationshipbetween inflammation and bone formation in inflammatory arthritis.

U2 - 10.1186/s13075-015-0531-7

DO - 10.1186/s13075-015-0531-7

M3 - Journal article

C2 - 25889670

VL - 17

SP - 1

EP - 18

JO - Arthritis Research & Therapy

JF - Arthritis Research & Therapy

SN - 1478-6354

IS - 43

ER -