Regulation of plasminogen activator inhibitor 1 expression in human osteoarthritic chondrocytes by fluid shear stress: role of protein kinase Calpha.
Arthritis Rheum
; 60(8): 2350-61, 2009 Aug.
Article
em En
| MEDLINE
| ID: mdl-19644850
ABSTRACT
OBJECTIVE:
To test a fluid flow system for the investigation of the influence of shear stress on expression of plasminogen activator inhibitor 1 (PAI-1) in human osteoarthritic (OA) articular chondrocytes (from lesional and nonlesional sites) and human SW-1353 chondrocytes.METHODS:
Human SW-1353 chondrocytes and OA and normal human articular chondrocytes were cultured on type II collagen-coated glass plates under static conditions or placed in a flow chamber to form a closed fluid-circulation system for exposure to different levels of shear stress (2-20 dyn/cm2). Real-time polymerase chain reaction was used to analyze PAI-1 gene expression, and protein kinase C (PKC) inhibitors and small interfering RNA were used to investigate the mechanism of shear stress-induced signal transduction in SW-1353 and OA (lesional and nonlesional) articular chondrocytes.RESULTS:
There was a significant reduction in PAI-1 expression in OA chondrocytes obtained from lesional sites compared with those obtained from nonlesional sites. In SW-1353 chondrocytes subjected to 2 hours of shear flow, moderate shear stresses (5 and 10 dyn/cm2) generated significant PAI-1 expression, which was regulated through PKCalpha phosphorylation and Sp-1 activation. These levels of shear stress also increased PAI-1 expression in articular chondrocytes from nonlesional sites and from normal healthy cartilage through the activation of PKCalpha and Sp-1 signal transduction, but no effect of these levels of fluid shear stress was observed on OA chondrocytes from lesional sites.CONCLUSION:
OA chondrocytes from lesional sites and those from nonlesional sites of human cartilage have differential responses to shear stress with regard to PAI-1 gene expression, and therefore diverse functional consequences can be observed.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Estresse Mecânico
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Cartilagem Articular
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Inibidor 1 de Ativador de Plasminogênio
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Condrócitos
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Osteoartrite do Joelho
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Proteína Quinase C-alfa
Limite:
Aged
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Aged80
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Humans
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article