Control vs. PGISp spine samples

OBJECTIVES: Ankylosing spondylitis (AS) is unique in its pathology where inflammation commences at the entheses before progressing to an osteoproliferative phenotype generating excessive bone formation that can result in joint fusion. The underlying mechanisms of this progression are poorly understood. Using the proteoglycan-induced spondylitis mouse (PGISp) model which displays spondylitis and eventual joint fusion following an initial inflammatory stimulus, we have characterised the structural and molecular changes that underlie disease progression METHODS: PGISp mice were characterised 12 weeks after initiation of inflammation using expression profiling. RESULTS: Microarray profiling showed genes involved in inflammation and immune-regulation were altered. Further, a number of genes specifically involved in bone regulation including other members of the Wnt pathway were also dysregulated. CONCLUSION: This study implicates the Wnt pathway as a likely mediator of the mechanism by which inflammation induces bony ankylosis in spondyloarthritis, raising the potential that therapies targeting this pathway may be effective in preventing this process. 4 unaffected spines vs. 4 spines from PGISp-affected mice