Evidence for species differences in the regulation of MMPs by all-trans retinoic acid in cytokine-stimulated chondrocytes.
Biorheology
; 45(3-4): 415-32, 2008.
Article
en En
| MEDLINE
| ID: mdl-18836242
In inflammatory conditions, chondrocytes produce large amounts of matrix metalloproteases (MMP) and nitric oxide (NO) thought to contribute to joint degradation. We tested the ability of all-trans retinoic acid (ATRA, a retinoic acid receptor (RAR) agonist) to modulate these inflammatory genes in chondrocytes from humans or rats, chosen as representative of animal models of arthritis. All RAR subtypes and RXR-alpha or -beta were expressed at the mRNA level in both species, although IL-1beta (10 ng/ml) inhibited RAR subtypes more markedly in rat than in human cells. ATRA (300 or 1000 nM) inhibited IL-1-induced expression of iNOS and nitrites level in both species, although the NO pathway was induced maximally in rat cells. ATRA displayed controversial effects on MMPs between rat and human chondrocytes, especially for MMP-9 expression. The effects of ATRA were irrelevant to the nuclear translocation of AP-1. The present data underlines that retinoids have a species-dependent impact on IL-1-induced responses in chondrocytes, suggesting that extrapolation of their pharmacological properties from animal cells has a poor relevance to clinical situation.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Tretinoina
/
Receptores de Ácido Retinoico
/
Factor de Transcripción AP-1
/
Condrocitos
/
Metaloproteinasas de la Matriz
/
Receptores X Retinoide
/
Interleucina-1beta
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Biorheology
Año:
2008
Tipo del documento:
Article
País de afiliación:
Francia
Pais de publicación:
Países Bajos