Introduction: Pathological bone changes differ considerably between inflammatory arthritic diseases and most
studies 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 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 CIA 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 inflammation occurred during the first two
weeks following the onset of clinical symptoms in the joint. Hereafter, the inflammation declined and remodelling
of formed bone dominated.
Global gene expression profiling showed simultaneous upregulation of genes related to bone changes and
inflammation 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 (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), 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 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, which
results in bony fusion within one to two weeks. This makes it a candidate model for investigating the relationship
between inflammation and bone formation in inflammatory arthritis.