PMID- 15325639 OWN - NLM STAT- MEDLINE DCOM- 20041217 LR - 20181130 IS - 1063-4584 (Print) IS - 1063-4584 (Linking) VI - 12 IP - 9 DP - 2004 Sep TI - Intermittent hydrostatic pressure inhibits matrix metalloproteinase and pro-inflammatory mediator release from human osteoarthritic chondrocytes in vitro. PG - 729-35 AB - 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 10 MPa at a frequency of 1 Hz for periods of 6, 12 and 24 h. 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 84/82 kDa 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 24 h, 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. FAU - Trindade, Michael C D AU - Trindade MC AD - Orthopaedic Research Laboratory, Stanford University School of Medicine, Stanford, CA 94305-5341, USA. FAU - Shida, Jun-ichi AU - Shida J FAU - Ikenoue, Takashi AU - Ikenoue T FAU - Lee, Mel S AU - Lee MS FAU - Lin, Eric Y AU - Lin EY FAU - Yaszay, Burt AU - Yaszay B FAU - Yerby, Scott AU - Yerby S FAU - Goodman, Stuart B AU - Goodman SB FAU - Schurman, David J AU - Schurman DJ FAU - Smith, R Lane AU - Smith RL LA - eng GR - AR 45788/AR/NIAMS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - Osteoarthritis Cartilage JT - Osteoarthritis and cartilage JID - 9305697 RN - 0 (CCL2 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Cytokines) RN - 0 (Interleukin-6) RN - EC 3.4.24.- (Matrix Metalloproteinases) SB - IM MH - Cartilage, Articular/*enzymology/immunology MH - Cells, Cultured MH - Chemokine CCL2/analysis/metabolism MH - Chondrocytes/immunology/*metabolism MH - Cytokines/*metabolism MH - Humans MH - Hydrostatic Pressure MH - Interleukin-6/analysis/metabolism MH - Matrix Metalloproteinases/analysis/*metabolism MH - Osteoarthritis/*enzymology/immunology MH - Statistics, Nonparametric EDAT- 2004/08/25 05:00 MHDA- 2004/12/18 09:00 CRDT- 2004/08/25 05:00 PHST- 2003/08/07 00:00 [received] PHST- 2004/05/14 00:00 [accepted] PHST- 2004/08/25 05:00 [pubmed] PHST- 2004/12/18 09:00 [medline] PHST- 2004/08/25 05:00 [entrez] AID - S1063458404000937 [pii] AID - 10.1016/j.joca.2004.05.008 [doi] PST - ppublish SO - Osteoarthritis Cartilage. 2004 Sep;12(9):729-35. doi: 10.1016/j.joca.2004.05.008.