The ghrelin paradox in the control of equine chondrocyte function: The good and the bad.
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 (10-10 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 and 10 mol/L) which did not recognize the GHS-R 1a. Low ghrelin concentrations reduced chondrocyte viability whereas 10 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.
Copyright © 2018 Elsevier Inc. All rights reserved.
Publication Date: 2018-03-08 PubMed ID: 29526750DOI: 10.1016/j.peptides.2018.03.003Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research investigates the role of a hormone called ghrelin in protecting cartilage cells, or chondrocytes, from inflammation and damage caused by conditions like osteoarthritis (OA). Different concentrations of ghrelin are tested, and its interaction with a specific receptor, termed GHS-R1a, is examined.
Objective and Research Methodology
- The objective of the study was to understand how ghrelin affects chondrocyte health and function, especially in the context of inflammatory diseases such as OA. The researchers examined interactions between ghrelin and a specific receptor called GHS-R1a.
- The experiments were carried out on cultured horse chondrocytes, which were tested under normal conditions and after being subjected to inflammation-causing LPS treatment.
- The cell viability and damage were examined using specific staining techniques, and the presence of the GHS-R1a receptor was confirmed via Western Blot, a commonly used technique in cell and molecular biology.
Results and Findings
- Low ghrelin concentrations were found to reduce chondrocyte viability, while a concentration of 10 mol/L was shown to protect the cells from LPS-induced damage.
- The protective effect of ghrelin was determined to be dependent on its interaction with the GHS-R1a receptor, as blocking this receptor significantly reduced ghrelin’s protective effect.
- The harmful effect of low ghrelin concentrations was shown to involve caspase activation — a process linked to cell death — and is speculated to be due to interaction with a different GHS-R type not recognized by either low ghrelin concentrations or a ghrelin variant called DAG.
- DAG was found to decrease chondrocyte viability in a dose-dependent manner and exacerbated LPS-induced damage.
- In summary, the research showed that ghrelin can protect chondrocytes against inflammation-induced damage via interaction with the GHS-R1a receptor.
Implications and Conclusions
- The results suggest that agonists, or activators, of the GHS-R1a receptor could potentially be used as local treatments for inflammatory joint diseases like OA.
- By understanding the role and functioning of ghrelin and its receptor GHS-R1a in chondrocyte health, it might be possible to develop treatments that can help protect against, slow down or even reverse cartilage damage in OA and similar disorders.
Cite This Article
APA
Ceriotti S, Consiglio AL, Casati L, Cremonesi F, Sibilia V, Ferrucci F.
(2018).
The ghrelin paradox in the control of equine chondrocyte function: The good and the bad.
Peptides, 103, 1-9.
https://doi.org/10.1016/j.peptides.2018.03.003 Publication
Researcher Affiliations
- Department of Health, Animal Science and Food Safety, School of Veterinary Medicine, Università degli Studi di Milano, Italy.
- Reproduction Unit, Large Animal Veterinary Hospital (Lodi), Università degli Studi di Milano, Italy.
- Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, Italy.
- Reproduction Unit, Large Animal Veterinary Hospital (Lodi), Università degli Studi di Milano, Italy; Department of Veterinary Medicine, Università degli Studi di Milano, Italy.
- Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, Italy. Electronic address: valeria.sibilia@unimi.it.
- Department of Health, Animal Science and Food Safety, School of Veterinary Medicine, Università degli Studi di Milano, Italy.
MeSH Terms
- Animals
- Cells, Cultured
- Chondrocytes / drug effects
- Chondrocytes / metabolism
- Ghrelin / metabolism
- Horses
- Lipopolysaccharides / toxicity
- Oligopeptides / pharmacology
- Osteoarthritis / chemically induced
- Osteoarthritis / metabolism
- Receptors, Ghrelin / antagonists & inhibitors
Citations
This article has been cited 1 times.- Vinod E, Lisha J J, Parasuraman G, Livingston A, Daniel AJ, Sathishkumar S. Evaluation of ghrelin as a distinguishing marker for human articular cartilage-derived chondrocytes and chondroprogenitors. J Clin Orthop Trauma 2023 Jun;41:102175.
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