Abstract:
OBJECTIVES:To investigate the secretion profiles of matrix metalloproteinases (MMP) and their inhibitors (TIMP) in synovial fluid-derived fibroblasts and to compare them with those of tissue-derived fibroblasts. METHODS:Fibroblast cultures established from synovial tissues (TSC) and fluids (FSC) of the same OA patients were stimulated with tumor necrosis factor(TNF)-alpha, interleukin(IL)-1alpha, IL-1beta, IL-6 and a combination of TNFalpha and IL-1beta. Cocultures of fibroblasts and cartilage were stimulated either with the cytokine combination or with osteoarthritic synovial fluid. Secretion of MMP-1, MMP-3, MMP-8, MMP-13, TIMP-1, and TIMP-2 was measured by enzyme-linked immunosorbent assay. Gelatin zymography and immunoblotting were performed to demonstrate enzyme activity. RESULTS:TNFalpha, IL-1alpha, and IL-1beta led to marked increases in MMP-1 and MMP-3 release (up to 4.2-fold and 547-fold, respectively) by synovial fibroblasts, whereas secretion of MMP-13 was induced by concomitant administration of TNFalpha and IL-1beta. Expression of intracellular MMP-8 was stimulated by cytokines, but adhesion of synovial fibroblasts to cartilage was required for the release. Throughout the study, significantly higher levels of secreted MMPs were observed in stimulated FSC compared to TSC cultures. Furthermore, increases in MMP secretion were not accompanied by increases in secreted TIMP-1 and TIMP-2, resulting in marked imbalances between enzyme and inhibitor levels. CONCLUSIONS:The results provide strong evidence for a significant impact of synovial-derived MMPs on cartilage destruction in OA. In this context, fibroblasts present in the synovial fluid appeared to play an outstanding role.
journal_name
Osteoarthritis Cartilagejournal_title
Osteoarthritis and cartilageauthors
Fuchs S,Skwara A,Bloch M,Dankbar Bdoi
10.1016/j.joca.2004.02.005keywords:
subject
Has Abstractpub_date
2004-05-01 00:00:00pages
409-18issue
5eissn
1063-4584issn
1522-9653pii
S1063458404000299journal_volume
12pub_type
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journal_title:Osteoarthritis and cartilage
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journal_title:Osteoarthritis and cartilage
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journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章,评审
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journal_title:Osteoarthritis and cartilage
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journal_title:Osteoarthritis and cartilage
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pub_type: 杂志文章,随机对照试验
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更新日期:2015-08-01 00:00:00
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journal_title:Osteoarthritis and cartilage
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doi:10.1016/j.joca.2015.08.005
更新日期:2016-02-01 00:00:00
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更新日期:2013-04-01 00:00:00
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更新日期:2016-06-01 00:00:00
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journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章
doi:10.1016/j.joca.2014.09.006
更新日期:2015-01-01 00:00:00
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journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章
doi:10.1016/j.joca.2020.01.017
更新日期:2020-06-01 00:00:00
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journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章
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更新日期:2006-10-01 00:00:00
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pub_type: 杂志文章
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更新日期:2010-09-01 00:00:00
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pub_type: 杂志文章
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更新日期:2005-04-01 00:00:00
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journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章
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更新日期:2015-02-01 00:00:00
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journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章
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更新日期:2007-04-27 00:00:00
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journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章
doi:10.1016/j.joca.2016.11.013
更新日期:2017-05-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/j.joca.2017.05.008
更新日期:2017-09-01 00:00:00
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journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章
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更新日期:2013-12-01 00:00:00
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journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章
doi:10.1016/j.joca.2008.07.013
更新日期:2009-03-01 00:00:00
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journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章
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更新日期:1999-07-01 00:00:00
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journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章,评审
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更新日期:2018-03-01 00:00:00
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pub_type: 杂志文章
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更新日期:2001-02-01 00:00:00
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journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章
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