Piascledine modulates the production of VEGF and TIMP-1 and reduces the invasiveness of rheumatoid arthritis synoviocytes

M. Cinelli, S. Guiducci, A. Del Rosso, A. Pignone, M. Del Rosso, G. Fibbi, S. Serratì, A. Gabrielli, R. Giacomelli, N. Piccardi, Marco Matucci Cerinic

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Abstract

Background: In rheumatoid arthritis (RA), hypertrophy of the synovial membrane generates a tumour-like pannus that invades the joint cavity and erodes cartilage and bone. Invasion of the extracellular matrix (ECM) is accompanied by angiogenesis, in which vascular endothelial growth factor (VEGF) and tissue inhibitors of metalloproteinases (TIMPs), produced by synoviocytes lining the pannus, have a primary role. Piascledine (PSD) is used in the treatment of osteoarthritis and has anti-inflammatory effects in vitro. Objective: To study the effects of PSD on levels of VEGF and TIMP-1 and chemoinvasion in RA synoviocytes and healthy controls. Methods: The effects of PSD 5, 10, and 20 μg/mL were evaluated, with/without interleukin-1β (IL-1β) and tumour necrosis factor-α (TNFα) 20 ng/mL, on synoviocytes. The levels of VEGF and TIMP-1 were assayed in the culture medium by enzyme-linked immunosorbent assay (ELISA). Chemoinvasion was measured by the Boyden chamber invasion assay. Results: RA synoviocytes treated with PSD showed, compared to basal, lower levels of VEGF (41080 ± 830 vs. 79210 ± 920 pg/106 cells, p <0.001) and increased levels of TIMP-1 (23540 ± 93.2 vs. 12860 ± 42.9 ng/106 cells, p <0.001). PSD decreased dose-dependently IL-1β and TNFα induced migration. Conclusions: In RA synoviocytes, and also to a lesser extent in control cells, PSD modulates VEGF and TIMP-1 and decreases chemoinvasion. PSD might have a role in the treatment of RA synovitis controlling invasiveness.

Original languageEnglish
Pages (from-to)346-350
Number of pages5
JournalScandinavian Journal of Rheumatology
Volume35
Issue number5
DOIs
Publication statusPublished - Oct 1 2006

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ASJC Scopus subject areas

  • Rheumatology
  • Immunology

Cite this

Cinelli, M., Guiducci, S., Del Rosso, A., Pignone, A., Del Rosso, M., Fibbi, G., Serratì, S., Gabrielli, A., Giacomelli, R., Piccardi, N., & Cerinic, M. M. (2006). Piascledine modulates the production of VEGF and TIMP-1 and reduces the invasiveness of rheumatoid arthritis synoviocytes. Scandinavian Journal of Rheumatology, 35(5), 346-350. https://doi.org/10.1080/03009740600709865