Glatiramer acetate (GA), the immunomodulatory drug, inhibits inflammatory mediators and collagen degradation in osteoarthritis (OA) cartilage.
Osteoarthritis Cartilage
; 19(9): 1158-64, 2011 Sep.
Article
en En
| MEDLINE
| ID: mdl-21745583
OBJECTIVE: Glatiramer acetate (GA), the generic name for Copaxone, an immunomodulatory agent, has been shown to induce interleukin-1 receptor antagonist (IL-1Ra) production in macrophages. We therefore tested the effects of GA on the catabolic activities of osteoarthritis (OA) chondrocytes. DESIGN: Primary human chondrocytes and OA cartilage explants were utilized in this study. IL-1Ra, pro-matrix metalloproteinase-13 (proMMP-13) and prostaglandin E(2) (PGE(2)) were estimated in the cell culture supernatants and in vitro MMP-13 activity was measured using fluorogenic substrate. TaqMan Real-Time quantitative polymerase chain reaction (RT-qPCR) was performed to estimate relative expression levels of genes. RESULTS: GA treatment significantly increased transcription and production of sIL-1Ra (P=0.001) in both culture models. Furthermore, addition of GA (100 µg) inhibited: (1) spontaneous collagen degradation as assayed by CTX II enzyme-linked immunosorbent assay (ELISA) [mean CTX II (ng/g cartilage)] in control was 7.79 [95% confidence interval (CI) 2.57-13.02]-3.415 (95% CI 0.81-6.02) (P=0.0286); (2) spontaneous proMMP-13 secretion [mean MMP-13 (ng/g cartilage)] in control was 16.98 (95% CI 7.739-26.23)-6.973 (95% CI 1.632-12.31) (P=0.0286); (3) production of IL-1ß-induced inflammatory mediators such as nitric oxide (NO) [mean NO (µM)] in IL-1 cultures was 11.47 (95% CI 7.10-15.83)-0.87 (95% CI 0.18-1.56) (P=0.0022); and (4) recombinant MMP-13 in vitro activity (15-25%; P=0.004). CONCLUSIONS: These data suggest that GA effects may be due to upregulation of IL-1Ra as well as direct inhibition of MMP-13 activity. Based on these studies, we propose that GA has potential for disease modifying properties in OA and should be evaluated in vivo in animal studies.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Péptidos
/
Cartílago Articular
/
Condrocitos
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Osteoartritis de la Rodilla
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Inmunosupresores
Límite:
Aged
/
Humans
/
Middle aged
Idioma:
En
Revista:
Osteoarthritis Cartilage
Asunto de la revista:
ORTOPEDIA
/
REUMATOLOGIA
Año:
2011
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Reino Unido