Antifibroproliferative effect of tenidap in chronic antigen-induced arthritis.
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 diclofenac-treated 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 beta1 (TGFbeta1) 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 (> or =25 microM) and down-regulated the expression and synthesis of FN in a dose-dependent manner (> or =1 microM). This antifibrotic effect was associated with a reduction of TGFbeta1 message.


CONCLUSIONS
Tenidap down-regulates the fibroproliferative changes typical of chronic arthritis, an effect that fits the profile of a disease-modifying agent for rheumatoid arthritis.
Sánchez-Pernaute
O
O
Fundación Jiménez Díaz, Universidad Autónoma, Madrid, Spain.
López-Armada
M J
MJ
Hernández
P
P
Palacios
I
I
Navarro
F
F
Martínez
J
J
Egido
J
J
Herrero-Beaumont
G
G
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects; D002908:Chronic Disease; D003094:Collagen / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D004008:Diclofenac / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D005109:Extracellular Matrix / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D006965:Hyperplasia / Q000473:pathology; D007211:Indoles / Q000097:blood / Q000494:pharmacology*; D000078183:Oxindoles; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D013583:Synovial Membrane / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics
D000894:Anti-Inflammatory Agents, Non-Steroidal; D017931:DNA Primers; D005353:Fibronectins; D007211:Indoles; D000078183:Oxindoles; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D004008:Diclofenac; D003094:Collagen; C062866:tenidap