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Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) Reduces Oxidative and Mechanical Stress-Evoked Matrix Degradation in Chondrifying Cell Cultures

Pituitary adenylate cyclase activating polypeptide (PACAP) is an endogenous neuropeptide also secreted by non-neural cells, including chondrocytes. PACAP signaling is involved in the regulation of chondrogenesis, but little is known about its connection to matrix turnover during cartilage formation...

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Autores principales: Szentléleky, Eszter, Szegeczki, Vince, Karanyicz, Edina, Hajdú, Tibor, Tamás, Andrea, Tóth, Gábor, Zákány, Róza, Reglődi, Dóra, Juhász, Tamás
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6337298/
https://www.ncbi.nlm.nih.gov/pubmed/30621194
http://dx.doi.org/10.3390/ijms20010168
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author Szentléleky, Eszter
Szegeczki, Vince
Karanyicz, Edina
Hajdú, Tibor
Tamás, Andrea
Tóth, Gábor
Zákány, Róza
Reglődi, Dóra
Juhász, Tamás
author_facet Szentléleky, Eszter
Szegeczki, Vince
Karanyicz, Edina
Hajdú, Tibor
Tamás, Andrea
Tóth, Gábor
Zákány, Róza
Reglődi, Dóra
Juhász, Tamás
author_sort Szentléleky, Eszter
collection PubMed
description Pituitary adenylate cyclase activating polypeptide (PACAP) is an endogenous neuropeptide also secreted by non-neural cells, including chondrocytes. PACAP signaling is involved in the regulation of chondrogenesis, but little is known about its connection to matrix turnover during cartilage formation and under cellular stress in developing cartilage. We found that the expression and activity of hyaluronidases (Hyals), matrix metalloproteinases (MMP), and aggrecanase were permanent during the course of chondrogenesis in primary chicken micromass cell cultures, although protein levels changed daily, along with moderate and relatively constant enzymatic activity. Next, we investigated whether PACAP influences matrix destructing enzyme activity during oxidative and mechanical stress in chondrogenic cells. Exogenous PACAP lowered Hyals and aggrecanase expression and activity during cellular stress. Expression and activation of the majority of cartilage matrix specific MMPs such as MMP1, MMP7, MMP8, and MMP13, were also decreased by PACAP addition upon oxidative and mechanical stress, while the activity of MMP9 seemed not to be influenced by the neuropeptide. These results suggest that application of PACAP can help to preserve the integrity of the newly synthetized cartilage matrix via signaling mechanisms, which ultimately inhibit the activity of matrix destroying enzymes under cellular stress. It implies the prospect that application of PACAP can ameliorate articular cartilage destruction in joint diseases.
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spelling pubmed-63372982019-01-22 Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) Reduces Oxidative and Mechanical Stress-Evoked Matrix Degradation in Chondrifying Cell Cultures Szentléleky, Eszter Szegeczki, Vince Karanyicz, Edina Hajdú, Tibor Tamás, Andrea Tóth, Gábor Zákány, Róza Reglődi, Dóra Juhász, Tamás Int J Mol Sci Article Pituitary adenylate cyclase activating polypeptide (PACAP) is an endogenous neuropeptide also secreted by non-neural cells, including chondrocytes. PACAP signaling is involved in the regulation of chondrogenesis, but little is known about its connection to matrix turnover during cartilage formation and under cellular stress in developing cartilage. We found that the expression and activity of hyaluronidases (Hyals), matrix metalloproteinases (MMP), and aggrecanase were permanent during the course of chondrogenesis in primary chicken micromass cell cultures, although protein levels changed daily, along with moderate and relatively constant enzymatic activity. Next, we investigated whether PACAP influences matrix destructing enzyme activity during oxidative and mechanical stress in chondrogenic cells. Exogenous PACAP lowered Hyals and aggrecanase expression and activity during cellular stress. Expression and activation of the majority of cartilage matrix specific MMPs such as MMP1, MMP7, MMP8, and MMP13, were also decreased by PACAP addition upon oxidative and mechanical stress, while the activity of MMP9 seemed not to be influenced by the neuropeptide. These results suggest that application of PACAP can help to preserve the integrity of the newly synthetized cartilage matrix via signaling mechanisms, which ultimately inhibit the activity of matrix destroying enzymes under cellular stress. It implies the prospect that application of PACAP can ameliorate articular cartilage destruction in joint diseases. MDPI 2019-01-04 /pmc/articles/PMC6337298/ /pubmed/30621194 http://dx.doi.org/10.3390/ijms20010168 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Szentléleky, Eszter
Szegeczki, Vince
Karanyicz, Edina
Hajdú, Tibor
Tamás, Andrea
Tóth, Gábor
Zákány, Róza
Reglődi, Dóra
Juhász, Tamás
Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) Reduces Oxidative and Mechanical Stress-Evoked Matrix Degradation in Chondrifying Cell Cultures
title Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) Reduces Oxidative and Mechanical Stress-Evoked Matrix Degradation in Chondrifying Cell Cultures
title_full Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) Reduces Oxidative and Mechanical Stress-Evoked Matrix Degradation in Chondrifying Cell Cultures
title_fullStr Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) Reduces Oxidative and Mechanical Stress-Evoked Matrix Degradation in Chondrifying Cell Cultures
title_full_unstemmed Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) Reduces Oxidative and Mechanical Stress-Evoked Matrix Degradation in Chondrifying Cell Cultures
title_short Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) Reduces Oxidative and Mechanical Stress-Evoked Matrix Degradation in Chondrifying Cell Cultures
title_sort pituitary adenylate cyclase activating polypeptide (pacap) reduces oxidative and mechanical stress-evoked matrix degradation in chondrifying cell cultures
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6337298/
https://www.ncbi.nlm.nih.gov/pubmed/30621194
http://dx.doi.org/10.3390/ijms20010168
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