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BMC Musculoskeletal Disorders
Published in: BMC Musculoskeletal Disorders 1/2015

Open Access 01-12-2015 | Research article

Treatment of a mouse model of ankylosing spondylitis with exogenous sclerostin has no effect on disease progression

Authors: Katelin R. Haynes, Hsu-Wen Tseng, Michaela Kneissel, Tibor T. Glant, Matthew A. Brown, Gethin P. Thomas

Published in: BMC Musculoskeletal Disorders | Issue 1/2015

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Abstract

Background

No treatment to date is available which specifically targets bone formation in ankylosing spondylitis (AS). Several recent studies have shown that sclerostin (SOST), a Wnt inhibitor specific to osteocytes and chondrocytes, is down-regulated in AS patients. This suggests Wnt signalling may be upregulated, and application of exogenous recombinant SOST (rSOST) may inhibit Wnt signalling and slow pathological bone formation.

Methods

The proteoglycan-induced spondylitis (PGISp) mouse model in which we have previously demonstrated downregulated SOST expression, was used for this study. Mice were injected with 2.5ug rSOST/day for a period of 8 weeks following induction of disease. Axial skeleton disease development was assessed by histology and skeletal changes examined using DEXA.

Results

rSOST treatment had no effect on peripheral or axial disease development, bone density or disease severity. Injected rSOST was stable over 8 h and residual levels were evident 24 h after injection, resulting in a cumulative increase in SOST serum levels over the treatment time course. Immunohistochemical examination of SOST levels within the joints in non-rSOST treated PGISp mice showed a significant decrease in the percentage of positive osteocytes in the unaffected joints compared to the affected joints, while no difference was seen in rSOST treated mice. This suggests that rSOST treatment increases the number of SOST-positive osteocytes in unaffected joints but not affected joints, despite having no impact on the number of joints affected by disease.

Conclusions

Although not disease-modifying, rSOST treatment did appear to regulate SOST levels in the joints suggesting biological activity. Further dose response studies are required and SOST may require modifications to improve its bone targeting ability in order to affect tissue formation to a meaningful level in this model.
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Metadata
Title
Treatment of a mouse model of ankylosing spondylitis with exogenous sclerostin has no effect on disease progression
Authors
Katelin R. Haynes
Hsu-Wen Tseng
Michaela Kneissel
Tibor T. Glant
Matthew A. Brown
Gethin P. Thomas
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Musculoskeletal Disorders / Issue 1/2015
Electronic ISSN: 1471-2474
DOI
https://doi.org/10.1186/s12891-015-0823-8

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