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 (10-7-10-11 mol/L) on equine primary cultured chondrocytes viability and necrosis in basal conditions and under LPS treatment (100 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, 10-7and 10-9 mol/L) which did not recognize the GHS-R 1a. Low ghrelin concentrations reduced chondrocyte viability whereas 10-7 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.

The ghrelin paradox in the control of equine chondrocyte function: The good and the bad / S. Ceriotti, A.L. Consiglio, L. Casati, F. Cremonesi, V. Sibilia, F. Ferrucci. - In: PEPTIDES. - ISSN 0196-9781. - 103(2018 Mar 08), pp. 1-9. [10.1016/j.peptides.2018.03.003]

The ghrelin paradox in the control of equine chondrocyte function: The good and the bad

Ceriotti, Serena;Consiglio, Anna Lange;Casati, Lavinia;Cremonesi, Fausto;Sibilia, Valeria;Ferrucci, Francesco
2018-03-08

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 (10-7-10-11 mol/L) on equine primary cultured chondrocytes viability and necrosis in basal conditions and under LPS treatment (100 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, 10-7and 10-9 mol/L) which did not recognize the GHS-R 1a. Low ghrelin concentrations reduced chondrocyte viability whereas 10-7 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.
Ghrelin; Osteoarthritis; Equine chondrocytes; GHSR1a; LPS cytotoxicity
Settore BIO/14 - Farmacologia
Settore VET/08 - Clinica Medica Veterinaria
Settore BIO/13 - Biologia Applicata
PEPTIDES
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/561844
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