The ghrelin paradox in the control of equine chondrocyte function: The good and the bad.
Peptides
; 103: 1-9, 2018 05.
Article
em En
| MEDLINE
| ID: mdl-29526750
ABSTRACT
Increasing evidence suggests a role for ghrelin in the control of articular inflammatory diseases like osteoarthritis (OA). In the present study we examined the ability of ghrelin to counteract LPS-induced necrosis and apoptosis of chondrocytes and the involvement of GH secretagogue receptor (GHS-R)1a in the protective action of ghrelin. The effects of ghrelin (10-7-10-11â¯mol/L) on equine primary cultured chondrocytes viability and necrosis in basal conditions and under LPS treatment (100â¯ng/ml) were detected by using both acridine orange/propidium iodide staining and annexin-5/propidium iodide staining. The presence of GHS-R1a on chondrocytes was detected by Western Blot. The involvement of the GHS-R1a in the ghrelin effect against LPS-induced cytotoxicity was examined by pretreating chondrocytes with D-Lys3-GHRP-6, a specific GHS-R1a antagonist, and by using des-acyl ghrelin (DAG, 10-7 and 10-9â¯mol/L) which did not recognize the GHS-R 1a. Low ghrelin concentrations reduced chondrocyte viability whereas 10-7â¯mol/L ghrelin protects against LPS-induced cellular damage. The protective effect of ghrelin depends on the interaction with the GHS-R1a since it is significantly reduced by D-Lys3-GHRP-6. The negative action of ghrelin involves caspase activation and could be due to an interaction with a GHS-R type different from the GHS-R1a recognized by both low ghrelin concentrations and DAG. DAG, in fact, induces a dose-dependent decrease in chondrocyte viability and exacerbates LPS-induced damage. These data indicate that ghrelin protects chondrocytes against LPS-induced damage via interaction with GHS-R1a and suggest the potential utility of local GHS-R1a agonist administration to treat articular inflammatory diseases such as OA.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oligopeptídeos
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Osteoartrite
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Lipopolissacarídeos
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Condrócitos
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Grelina
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Receptores de Grelina
Limite:
Animals
Idioma:
En
Revista:
Peptides
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Itália