Kinetics of gene expression and bone remodelling in the clinical phase of collagen-induced XXXX .

@entity1 @entity32 @entity625 @entity309 @entity16240 @entity1753 @entity79 @entity16699 @entity12635 @entity1096 @entity15714 @entity6861
INTRODUCTION: Pathological bone changes differ considerably between inflammatory arthritic diseases and most studies have focused on @entity79 . @entity1753 ( @entity1753 ) is a model for @entity309 , which, in addition to @entity79 , demonstrates bone formation at the time of clinical manifestations. The objective of this study was to use this model to characterise the histological and molecular changes in bone remodelling, and relate these to the clinical disease development. METHODS: A histological and gene expression profiling time-course study on bone remodelling in @entity1753 was linked to onset of clinical symptoms. Global gene expression was studied with a gene chip array system. RESULTS: The main histopathological changes in bone structure and @entity32 occurred during the first two weeks following the onset of clinical symptoms in the joint. Hereafter, the @entity32 declined and remodelling of formed bone dominated. Global gene expression profiling showed simultaneous upregulation of genes related to bone changes and @entity32 in week 0 to 2 after onset of clinical disease. Furthermore, we observed time-dependent expression of genes involved in early and late osteoblast differentiation and function, which mirrored the histopathological bone changes. The differentially expressed genes belong to the bone morphogenetic pathway ( @entity6861 ) and, in addition, include the osteoblast markers @entity16240 ( @entity16240 ), bone @entity16699 protein (Bglap1), and @entity1096 ( @entity1096 ). Pregnancy-associated protein A ( @entity15714 ) and @entity12635 ( @entity12635 ), differentially expressed in the early disease phase, are proposed to participate in bone formation, and we suggest that they play a role in early bone formation in the @entity1753 model. Comparison to @entity1 genome-wide association studies (GWAS) revealed differential expression of several genes associated with @entity1 @entity625 . CONCLUSIONS: In the @entity1753 model, bone formation in the joint starts shortly after onset of clinical symptoms, which results in bony fusion within one to two weeks. This makes it a candidate model for investigating the relationship between @entity32 and bone formation in @entity625 .
