Early anti-inflammatory intervention ameliorates axial disease in the proteoglycan-induced spondylitis mouse model of ankylosing spondylitis

Tseng, Hsu-Wen, Glant, Tibor T., Brown, Matthew A., Kenna, Tony J., Thomas, Gethin P. and Pettit, Allison R. (2017) Early anti-inflammatory intervention ameliorates axial disease in the proteoglycan-induced spondylitis mouse model of ankylosing spondylitis. BMC Musculoskeletal Disorders, 18 1: . doi:10.1186/s12891-017-1600-7


Author Tseng, Hsu-Wen
Glant, Tibor T.
Brown, Matthew A.
Kenna, Tony J.
Thomas, Gethin P.
Pettit, Allison R.
Title Early anti-inflammatory intervention ameliorates axial disease in the proteoglycan-induced spondylitis mouse model of ankylosing spondylitis
Journal name BMC Musculoskeletal Disorders   Check publisher's open access policy
ISSN 1471-2474
Publication date 2017-05-30
Year available 2017
Sub-type Article (original research)
DOI 10.1186/s12891-017-1600-7
Open Access Status DOI
Volume 18
Issue 1
Total pages 9
Place of publication London, United Kingdom
Publisher BioMed Central
Language eng
Abstract Ankylosing spondylitis (AS) is characterised by immune-mediated arthritis and osteoproliferation, ultimately leading to joint ankylosis. Whether inflammation is necessary for osteoproliferation is controversial, fuelled by the unclear efficacy of anti-inflammatory treatments on radiographic progression. In proteoglycan-induced spondylitis (PGISp), a mouse model of AS, inflammation is the prerequisite for osteoproliferation as osteoproliferation was only observed following inflammation-driven intervertebral disc (IVD) destruction. We hypothesised that early intervention with a potent anti-inflammatory therapy would protect IVD integrity and consequently alter disease progression.
Formatted abstract
Background: Ankylosing spondylitis (AS) is characterised by immune-mediated arthritis and osteoproliferation, ultimately leading to joint ankylosis. Whether inflammation is necessary for osteoproliferation is controversial, fuelled by the unclear efficacy of anti-inflammatory treatments on radiographic progression. In proteoglycan-induced spondylitis (PGISp), a mouse model of AS, inflammation is the prerequisite for osteoproliferation as osteoproliferation was only observed following inflammation-driven intervertebral disc (IVD) destruction. We hypothesised that early intervention with a potent anti-inflammatory therapy would protect IVD integrity and consequently alter disease progression.

Methods: PGISp mice received vehicle or a combination of etanercept (ETN) plus prednisolone (PRD) therapy for 2 or 6 weeks initiated at an early disease stage. Peripheral arthritis was scored longitudinally. Spinal disease was assessed using a semi-quantitative histological scoring regimen including inflammation, joint destruction and excessive tissue formation.

Results: ETN + PRD therapy significantly delayed the onset of peripheral arthritis. IVD integrity was significantly protected when treatment was commenced in early disease. Six-weeks of treatment resulted in trends towards reductions in intervertebral joint damage and excessive tissue formation. IVD score distribution was dichotomized, likely reflecting the extent of axial disease at initiation of therapy. In the sub-group of mice with high IVD destruction scores, ETN + PRD treatment significantly reduced IVD destruction severity, inflammation and bone erosion and reduced cartilage damage and excessive tissue formation.


Conclusions:
Early intervention with anti-inflammatory treatment not only improved inflammatory symptoms but also ameliorated structural damage of spine in PGISp mice. This preclinical observation suggests that early anti-inflammatory intervention may slow radiographic progression in AS patients.
Keyword Ankylosing spondylitis
Early intervention
Osteoproliferation
Proteoglycan-induced spondylitis mouse model
Spondyloarthropathy
Q-Index Code C1
Grant ID R01 AR062991
Institutional Status UQ
Additional Notes Article number 228

Document type: Journal Article
Sub-type: Article (original research)
Collections: Mater Research Institute-UQ (MRI-UQ)
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UQ Diamantina Institute Publications
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