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Aggrecanase cleavage in juvenile idiopathic arthritis patients is minimally detected in the aggrecan interglobular domain but robust at the aggrecan C-terminus.
MedLine Citation:
PMID:  22886575     Owner:  NLM     Status:  Publisher    
OBJECTIVE: To understand aggrecan degradation in juvenile idiopathic arthritis (JIA), the pattern and abundance of aggrecan fragments in synovial fluid aspirates from JIA patients were analysed and compared with aggrecan fragments in synovial fluids from patients with other arthritides, juvenile knee injury and a knee-healthy reference group. METHODS: The concentration of sulphated glycosaminoglycans in synovial fluid was measured by the Alcian blue precipitation assay. Aggrecan fragments were purified by dissociative CsCl density gradient centrifugation, deglycosylated and analysed by Western blot using antibodies specific for either aggrecanase-derived ARGS, SELE and KEEE neoepitopes, or the aggrecan G3-domain. RESULTS: The concentration of sulphated glycosaminoglycans in JIA synovial fluids was significantly lower compared with the levels in fluids from OA (P<0.001), juvenile knee injury (P=0.006) and knee-healthy reference (P=0.022) groups. Western blot analysis detected KEEE, SELE, and G3 fragments generated by aggrecanase cleavage in the chondroitin sulphate-rich region of JIA aggrecan. The pattern of JIA aggrecan fragments was not identical to that in synovial fluids pooled from OA patients, although there were notable similarities. Surprisingly, aggrecanase-derived ARGS fragments were barely detectable in the JIA synovial fluids, in marked contrast to the levels of ARGS fragments in OA synovial fluids. CONCLUSIONS: Aggrecanases appear to cleave minimally in the interglobular domain of aggrecan in JIA patients despite robust levels of cleavage in aggrecan's chondroitin-sulphate rich region. The results suggest that unlike other arthritides, aggrecanase cleavage in the aggrecan interglobular domain might not be a major pathogenic event in JIA. © 2012 American College of Rheumatology.
André Struglics; L Stefan Lohmander; Karena Last; Jonathan Akikusa; Roger Allen; Amanda J Fosang
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-8
Journal Detail:
Title:  Arthritis and rheumatism     Volume:  -     ISSN:  1529-0131     ISO Abbreviation:  Arthritis Rheum.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370605     Medline TA:  Arthritis Rheum     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 by the American College of Rheumatology.
Department of Orthopaedics, Clinical Sciences Lund, Lund University, Lund, Sweden.
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