Open AccessAntifibroproliferative effect of tenidap in chronic antigen‐induced arthritis
Author(s) -
SánchezPernaute Olga,
LópezArmada Maria José,
Hernández Purificación,
Palacios Itziar,
Egido Jesüs,
HerreroBeaumont Gabriel,
Navarro Francisco,
Martinez Javier
Publication year - 1997
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.1780401208
Subject(s) - synovial membrane , medicine , arthritis , fibronectin , rheumatoid arthritis , antigen , extracellular matrix , in vitro , hyperplasia , immunology , chemistry , biochemistry
Abstract Objective . To determine whether tenidap regulates extracellular matrix metabolism in chronic arthritis. Methods . Antigen arthritis was induced in the knees of 30 rabbits. Animals were distributed into 3 groups: untreated, tenidap‐treated, and diclofenactreated rabbits. Three weeks after disease induction, synovial membranes were extracted and processed for histopathologic examination and detection of type I collagen (CI) and fibronectin (FN) by immunoperoxidase. Simultaneously, we analyzed the in vitro effect of tenidap on healthy synovial cell (SC) proliferation, FN expression and synthesis, and expression of transforming growth factor β1 (TGFβ1) messenger RNA. Results . Untreated animals showed synovial lining hyperplasia, cellular infiltration at the sublining, and increased deposition of matrix proteins. These findings were not apparent in tenidap‐treated rabbits, where CI and FN had the same distribution as in healthy synovial membranes. In vitro, tenidap inhibited SC proliferation (⩾25 μ M ) and down‐regulated the expression and synthesis of FN in a dose‐dependent manner (⩾1 μ M ). This antifibrotic effect was associated with a reduction of TGFβ1 message. Conclusion . Tenidap down‐regulates the fibroproliferative changes typical of chronic arthritis, an effect that fits the profile of a disease‐modifying agent for rheumatoid arthritis.