Excessive bone formation in a mouse model of ankylosing spondylitis is associated with decreases in Wnt pathway inhibitors

Haynes, Katelin R., Pettit, Allison R., Duan, Ran, Tseng, Hsu-Wen, Glant, Tibor T., Brown, Matthew A. and Thomas, Gethin P. (2012) Excessive bone formation in a mouse model of ankylosing spondylitis is associated with decreases in Wnt pathway inhibitors. Arthritis Research & Therapy, 14 6: R253.1-R253.12. doi:10.1186/ar4096

Author Haynes, Katelin R.
Pettit, Allison R.
Duan, Ran
Tseng, Hsu-Wen
Glant, Tibor T.
Brown, Matthew A.
Thomas, Gethin P.
Title Excessive bone formation in a mouse model of ankylosing spondylitis is associated with decreases in Wnt pathway inhibitors
Journal name Arthritis Research & Therapy   Check publisher's open access policy
ISSN 1478-6354
Publication date 2012-11-22
Sub-type Article (original research)
DOI 10.1186/ar4096
Open Access Status DOI
Volume 14
Issue 6
Start page R253.1
End page R253.12
Total pages 12
Place of publication London, United Kingdom
Publisher BioMed Central
Collection year 2013
Language eng
Formatted abstract
Introduction: 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. Recent work has suggested that changes in Wnt signalling, a key bone regulatory pathway, may contribute to joint ankylosis in AS. Using the proteoglycan-induced spondylitis (PGISp) mouse 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 histology, immunohistochemistry (IHC) and expression profiling.

Results: Inflammation initiated at the periphery of the intervertebral discs progressing to disc destruction followed by massively excessive cartilage and bone matrix formation, as demonstrated by toluidine blue staining and IHC for collagen type I and osteocalcin, leading to syndesmophyte formation. Expression levels of DKK1 and SOST, Wnt signalling inhibitors highly expressed in joints, were reduced by 49% and 63% respectively in the spine PGISp compared with control mice (P < 0.05) with SOST inhibition confirmed by IHC. 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.

Conclusions: 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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Article number R253

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2013 Collection
UQ Diamantina Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 25 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 30 times in Scopus Article | Citations
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Created: Tue, 12 Feb 2013, 13:04:58 EST by Mrs Maureen Pollard on behalf of Paediatrics & Child Health - RBWH