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Leptin enhances MMP-1, MMP-3 and MMP-13 production in human osteoarthritic cartilage and correlates with MMP-1 and MMP-3 in synovial fluid from OA patients.
MedLine Citation:
PMID:  21345293     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
OBJECTIVES: In the present study, we investigated the role of adipocytokine leptin in the pathogenesis of osteoarthritis (OA) by measuring its effects on matrix metalloproteinase (MMP) production in human OA cartilage. In addition, the correlations between leptin and MMP concentrations in synovial fluid from OA patients were studied.
METHODS: Cartilage tissue obtained from leftover pieces of total knee replacement surgery from patients with OA was used in the experiments. Production of collagenases MMP-1, MMP-8 and MMP-13, and stromelysin-1 (MMP-3) in the cartilage was measured by immunoassay and the signalling pathways were explored by pharmacological means. In addition, synovial fluid samples were collected from 84 OA patients undergoing knee replacement surgery. The concentrations of leptin and MMPs in synovial fluid were measured by immunoassay.
RESULTS: Leptin alone and in combination with IL-1β enhanced production of MMP-1, MMP-3, and MMP-13 in human OA cartilage, while MMP-8 concentrations remained undetectable. The effects of leptin on MMP-1, MMP-3 and MMP-13 production were mediated through transcription factor NF-κβ, and through protein kinase C and MAP kinase pathways. Interestingly, leptin concentrations in synovial fluid from OA patients correlated positively with MMP-3 (r=0.51, p<0.001) and MMP-1 (r=0.41, p<0.001) levels.
CONCLUSIONS: To our knowledge, this is the first study to show that leptin up-regulates MMP-1 and MMP-3 production in human OA cartilage and correlates positively to MMP-1 and MMP-3 in synovial fluid from OA patients. The findings suggest that leptin has catabolic effects in OA joints by increasing MMP production in cartilage.
Authors:
Anna Koskinen; Katriina Vuolteenaho; Riina Nieminen; Teemu Moilanen; Eeva Moilanen
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Publication Detail:
Type:  Journal Article     Date:  2011-02-23
Journal Detail:
Title:  Clinical and experimental rheumatology     Volume:  29     ISSN:  0392-856X     ISO Abbreviation:  Clin. Exp. Rheumatol.     Publication Date:    2011 Jan-Feb
Date Detail:
Created Date:  2011-02-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8308521     Medline TA:  Clin Exp Rheumatol     Country:  Italy    
Other Details:
Languages:  eng     Pagination:  57-64     Citation Subset:  IM    
Affiliation:
The Immunopharmacology Research Group, Medical School, University of Tampere and Research Unit, Tampere University Hospital, Tampere, Finland. anna.koskinen@uta.fi.
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