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COMP and TSP-4: Functional Roles in Articular Cartilage and Relevance in Osteoarthritis

Osteoarthritis (OA) is a slow-progressing joint disease, leading to the degradation and remodeling of the cartilage extracellular matrix (ECM). The usually quiescent chondrocytes become reactivated and accumulate in cell clusters, become hypertrophic, and intensively produce not only degrading enzym...

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Autores principales: Maly, Kathrin, Andres Sastre, Enrique, Farrell, Eric, Meurer, Andrea, Zaucke, Frank
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956748/
https://www.ncbi.nlm.nih.gov/pubmed/33668140
http://dx.doi.org/10.3390/ijms22052242
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author Maly, Kathrin
Andres Sastre, Enrique
Farrell, Eric
Meurer, Andrea
Zaucke, Frank
author_facet Maly, Kathrin
Andres Sastre, Enrique
Farrell, Eric
Meurer, Andrea
Zaucke, Frank
author_sort Maly, Kathrin
collection PubMed
description Osteoarthritis (OA) is a slow-progressing joint disease, leading to the degradation and remodeling of the cartilage extracellular matrix (ECM). The usually quiescent chondrocytes become reactivated and accumulate in cell clusters, become hypertrophic, and intensively produce not only degrading enzymes, but also ECM proteins, like the cartilage oligomeric matrix protein (COMP) and thrombospondin-4 (TSP-4). To date, the functional roles of these newly synthesized proteins in articular cartilage are still elusive. Therefore, we analyzed the involvement of both proteins in OA specific processes in in vitro studies, using porcine chondrocytes, isolated from femoral condyles. The effect of COMP and TSP-4 on chondrocyte migration was investigated in transwell assays and their potential to modulate the chondrocyte phenotype, protein synthesis and matrix formation by immunofluorescence staining and immunoblot. Our results demonstrate that COMP could attract chondrocytes and may contribute to a repopulation of damaged cartilage areas, while TSP-4 did not affect this process. In contrast, both proteins similarly promoted the synthesis and matrix formation of collagen II, IX, XII and proteoglycans, but inhibited that of collagen I and X, resulting in a stabilized chondrocyte phenotype. These data suggest that COMP and TSP-4 activate mechanisms to protect and repair the ECM in articular cartilage.
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spelling pubmed-79567482021-03-16 COMP and TSP-4: Functional Roles in Articular Cartilage and Relevance in Osteoarthritis Maly, Kathrin Andres Sastre, Enrique Farrell, Eric Meurer, Andrea Zaucke, Frank Int J Mol Sci Article Osteoarthritis (OA) is a slow-progressing joint disease, leading to the degradation and remodeling of the cartilage extracellular matrix (ECM). The usually quiescent chondrocytes become reactivated and accumulate in cell clusters, become hypertrophic, and intensively produce not only degrading enzymes, but also ECM proteins, like the cartilage oligomeric matrix protein (COMP) and thrombospondin-4 (TSP-4). To date, the functional roles of these newly synthesized proteins in articular cartilage are still elusive. Therefore, we analyzed the involvement of both proteins in OA specific processes in in vitro studies, using porcine chondrocytes, isolated from femoral condyles. The effect of COMP and TSP-4 on chondrocyte migration was investigated in transwell assays and their potential to modulate the chondrocyte phenotype, protein synthesis and matrix formation by immunofluorescence staining and immunoblot. Our results demonstrate that COMP could attract chondrocytes and may contribute to a repopulation of damaged cartilage areas, while TSP-4 did not affect this process. In contrast, both proteins similarly promoted the synthesis and matrix formation of collagen II, IX, XII and proteoglycans, but inhibited that of collagen I and X, resulting in a stabilized chondrocyte phenotype. These data suggest that COMP and TSP-4 activate mechanisms to protect and repair the ECM in articular cartilage. MDPI 2021-02-24 /pmc/articles/PMC7956748/ /pubmed/33668140 http://dx.doi.org/10.3390/ijms22052242 Text en © 2021 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
Maly, Kathrin
Andres Sastre, Enrique
Farrell, Eric
Meurer, Andrea
Zaucke, Frank
COMP and TSP-4: Functional Roles in Articular Cartilage and Relevance in Osteoarthritis
title COMP and TSP-4: Functional Roles in Articular Cartilage and Relevance in Osteoarthritis
title_full COMP and TSP-4: Functional Roles in Articular Cartilage and Relevance in Osteoarthritis
title_fullStr COMP and TSP-4: Functional Roles in Articular Cartilage and Relevance in Osteoarthritis
title_full_unstemmed COMP and TSP-4: Functional Roles in Articular Cartilage and Relevance in Osteoarthritis
title_short COMP and TSP-4: Functional Roles in Articular Cartilage and Relevance in Osteoarthritis
title_sort comp and tsp-4: functional roles in articular cartilage and relevance in osteoarthritis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956748/
https://www.ncbi.nlm.nih.gov/pubmed/33668140
http://dx.doi.org/10.3390/ijms22052242
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