1. Intermittent hydrostatic pressure inhibits matrix metalloproteinase and pro-inflammatory mediator release from human osteoarthritic chondrocytes in vitro
- Author
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R. Lane Smith, Eric Y. Lin, Jun-ichi Shida, Takashi Ikenoue, Scott A. Yerby, Burt Yaszay, David J. Schurman, Stuart B. Goodman, Mel S. Lee, and Michael C. D. Trindade
- Subjects
Cartilage, Articular ,Hydrostatic pressure ,Biomedical Engineering ,Matrix (biology) ,Matrix metalloproteinase ,Mechanical loading ,Statistics, Nonparametric ,Chondrocyte ,Andrology ,Chondrocytes ,Rheumatology ,In vivo ,Human chondrocytes ,Osteoarthritis ,Hydrostatic Pressure ,medicine ,Humans ,Orthopedics and Sports Medicine ,Zymography ,Cells, Cultured ,Chemokine CCL2 ,Interleukin-6 ,Chemistry ,Cartilage ,Matrix Metalloproteinases ,In vitro ,medicine.anatomical_structure ,Immunology ,Cytokines - Abstract
Objective This study tested the hypothesis that intermittent hydrostatic pressure applied to human osteoarthritic chondrocytes modulates matrix metalloproteinase and pro-inflammatory mediator release in vitro . Design Human osteoarthritic articular chondrocytes were isolated and cultured as primary high-density monolayers. For testing, chondrocyte cultures were transferred to serum-free medium and maintained without loading or with exposure to intermittent hydrostatic pressure (IHP) at 10MPa at a frequency of 1Hz for periods of 6, 12 and 24h. Levels of matrix metalloproteinase-2, -9 (MMP-2, -9), tissue inhibitor of metalloproteinase-1 (TIMP-1), and the pro-inflammatory mediators, interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1), released into the culture medium were assessed by ELISA. Matrix metalloproteinase activity was confirmed by zymographic analysis. Results In the absence of IHP, levels of MMP-2, TIMP-1, IL-6, and MCP-1 in the chondrocyte culture medium increased in a time-dependent manner. Application of IHP decreased MMP-2 levels at all time periods tested, relative to unloaded control cultures maintained for the same time periods. Although 84/82kDa bands were faintly detectable by zymography, MMP-9 levels were not quantifiable in medium from loaded or unloaded cultures by ELISA. TIMP-1 levels were not altered in response to IHP at any time period tested. IL-6 and MCP-1 levels decreased in cultures exposed to IHP at 12 and 24h, relative to unloaded control cultures maintained for the same time periods. Conclusion IHP decreased release of MMP-2, IL-6 and MCP-1 by osteoarthritic chondrocytes in vitro suggesting that pressure influences cartilage stability by modulating chondrocyte expression of these degradative and pro-inflammatory proteins in vivo .
- Published
- 2004
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