Reduction of cytokine-induced expression and activity of MMP-1 and MMP-13 by mechanical strain in MH7A rheumatoid synovial cells

Hui Bin Sun, Hiroki Yokota

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

Excessive mechanical load induces harmful outcomes for joint diseases, such as osteoarthritis and rheumatoid arthritis, but physical stimuli at appropriate intensity are essential for growth and maintenance of bone and articular cartilage. Using a fibroblast-like synoviocyte cell line derived from a patient with rheumatoid arthritis, we examined the effects of gentle cyclic strain, focusing on the expression and activity of matrix metalloproteinase-1 (MMP-1) and MMP-13. Synovial cells were cultured on a collagen-coated agar block and exposed to 2% cyclic strain at 6 rev./min for 1 h. Expression of MMP-1 and MMP-13 was assayed using semi-quantitative and real-time PCR, as well as immunoblotting. Their activity was measured using spectrofluorometry and zymography. The results showed that the cyclic strain reduced the mRNA and protein levels of MMP-1 and MMP-13, and that both collagenase and gelatinase activity was decreased under the strain. The reduction in MMP activity by the cyclic strain was not achieved by the transcriptional inhibitor, actinomycin D. In the presence of proinflammatory cytokines, such as IL-1β and TNF-α, the strain reduced the cytokine-induced expression and activities of MMPs. Interestingly, the strain elevated the mRNA level of tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2. These results support a potential role of mechanical strain in down-regulating the cytokine-mediated proteolytic processes in synoviocytes.

Original languageEnglish (US)
Pages (from-to)263-270
Number of pages8
JournalMatrix Biology
Volume21
Issue number3
DOIs
StatePublished - May 21 2002
Externally publishedYes

Keywords

  • Cyclic strain
  • Interleukin-1 (IL-1)
  • Matrix metalloproteinase
  • Rheumatoid arthritis
  • Synovial cells
  • Tissue inhibitor of metalloproteinase
  • Tumor necrosis factor-α (TNF-α)

ASJC Scopus subject areas

  • Molecular Biology

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