Low dose of indomethacin and Hedgehog signaling inhibitor administration synergistically attenuates cartilage damage in osteoarthritis by controlling chondrocytes pyroptosis.
Gene
; 712: 143959, 2019 Sep 05.
Article
em En
| MEDLINE
| ID: mdl-31278964
ABSTRACT
Blockade of Hedgehog signaling can prevent osteoarthritis (OA) syndromes. However, the amelioration of related inflammation condition is limited. The purpose of this study was to observe the effect of combined use of Hedgehog signaling inhibitor GANT-61 and common clinical anti-inflammatory drug indomethacin on cartilage injury and inflammation in experimental OA mice. We found that GANT-61 and indomethacin synergistically attenuate cartilage damage and serum levels of inflammatory cytokines TNF-α, IL-2 and IL-6 in OA mice. Moreover, in vitro treatment of GANT-61 and indomethacin synergistically reduced the mRNA expression of TNF-α, IL-2 and IL-6 in lipopolysaccharide (LPS)-stimulated C28/I2 chondrocytes. Mechasnistic studies showed that GANT-61 and indomethacin synergistically attenuate the expressions of cell pyroptosis-related genes caspase-1, IL-1ß and IL-18 at mRNA and protein level. To conclude, our study showed that GANT-61 and indomethacin had a synergistically ameliorating effect on osteoarthritis by mediating chondrocytes pyroptosis.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Osteoartrite
/
Piridinas
/
Pirimidinas
/
Cartilagem
/
Indometacina
/
Condrócitos
/
Proteínas Hedgehog
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Gene
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
China