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Decreased metalloproteinase production as a response to mechanical pressure in human cartilage: a mechanism for homeostatic regulation

Articular cartilage is optimised for bearing mechanical loads. Chondrocytes are the only cells present in mature cartilage and are responsible for the synthesis and integrity of the extracellular matrix. Appropriate joint loads stimulate chondrocytes to maintain healthy cartilage with a concrete pro...

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Autores principales: Monfort, Jordi, Garcia-Giralt, Natalia, López-Armada, María J, Monllau, Joan C, Bonilla, Angeles, Benito, Pere, Blanco, Francisco J
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1779454/
https://www.ncbi.nlm.nih.gov/pubmed/16972994
http://dx.doi.org/10.1186/ar2042
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author Monfort, Jordi
Garcia-Giralt, Natalia
López-Armada, María J
Monllau, Joan C
Bonilla, Angeles
Benito, Pere
Blanco, Francisco J
author_facet Monfort, Jordi
Garcia-Giralt, Natalia
López-Armada, María J
Monllau, Joan C
Bonilla, Angeles
Benito, Pere
Blanco, Francisco J
author_sort Monfort, Jordi
collection PubMed
description Articular cartilage is optimised for bearing mechanical loads. Chondrocytes are the only cells present in mature cartilage and are responsible for the synthesis and integrity of the extracellular matrix. Appropriate joint loads stimulate chondrocytes to maintain healthy cartilage with a concrete protein composition according to loading demands. In contrast, inappropriate loads alter the composition of cartilage, leading to osteoarthritis (OA). Matrix metalloproteinases (MMPs) are involved in degradation of cartilage matrix components and have been implicated in OA, but their role in loading response is unclear. With this study, we aimed to elucidate the role of MMP-1 and MMP-3 in cartilage composition in response to mechanical load and to analyse the differences in aggrecan and type II collagen content in articular cartilage from maximum- and minimum-weight-bearing regions of human healthy and OA hips. In parallel, we analyse the apoptosis of chondrocytes in maximal and minimal load areas. Because human femoral heads are subjected to different loads at defined sites, both areas were obtained from the same hip and subsequently evaluated for differences in aggrecan, type II collagen, MMP-1, and MMP-3 content (enzyme-linked immunosorbent assay) and gene expression (real-time polymerase chain reaction) and for chondrocyte apoptosis (flow cytometry, bcl-2 Western blot, and mitochondrial membrane potential analysis). The results showed that the load reduced the MMP-1 and MMP-3 synthesis (p < 0.05) in healthy but not in OA cartilage. No significant differences between pressure areas were found for aggrecan and type II collagen gene expression levels. However, a trend toward significance, in the aggrecan/collagen II ratio, was found for healthy hips (p = 0.057) upon comparison of pressure areas (loaded areas > non-loaded areas). Moreover, compared with normal cartilage, OA cartilage showed a 10- to 20-fold lower ratio of aggrecan to type II collagen, suggesting that the balance between the major structural proteins is crucial to the integrity and function of the tissue. Alternatively, no differences in apoptosis levels between loading areas were found – evidence that mechanical load regulates cartilage matrix composition but does not affect chondrocyte viability. The results suggest that MMPs play a key role in regulating the balance of structural proteins of the articular cartilage matrix according to local mechanical demands.
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spelling pubmed-17794542007-01-19 Decreased metalloproteinase production as a response to mechanical pressure in human cartilage: a mechanism for homeostatic regulation Monfort, Jordi Garcia-Giralt, Natalia López-Armada, María J Monllau, Joan C Bonilla, Angeles Benito, Pere Blanco, Francisco J Arthritis Res Ther Research Article Articular cartilage is optimised for bearing mechanical loads. Chondrocytes are the only cells present in mature cartilage and are responsible for the synthesis and integrity of the extracellular matrix. Appropriate joint loads stimulate chondrocytes to maintain healthy cartilage with a concrete protein composition according to loading demands. In contrast, inappropriate loads alter the composition of cartilage, leading to osteoarthritis (OA). Matrix metalloproteinases (MMPs) are involved in degradation of cartilage matrix components and have been implicated in OA, but their role in loading response is unclear. With this study, we aimed to elucidate the role of MMP-1 and MMP-3 in cartilage composition in response to mechanical load and to analyse the differences in aggrecan and type II collagen content in articular cartilage from maximum- and minimum-weight-bearing regions of human healthy and OA hips. In parallel, we analyse the apoptosis of chondrocytes in maximal and minimal load areas. Because human femoral heads are subjected to different loads at defined sites, both areas were obtained from the same hip and subsequently evaluated for differences in aggrecan, type II collagen, MMP-1, and MMP-3 content (enzyme-linked immunosorbent assay) and gene expression (real-time polymerase chain reaction) and for chondrocyte apoptosis (flow cytometry, bcl-2 Western blot, and mitochondrial membrane potential analysis). The results showed that the load reduced the MMP-1 and MMP-3 synthesis (p < 0.05) in healthy but not in OA cartilage. No significant differences between pressure areas were found for aggrecan and type II collagen gene expression levels. However, a trend toward significance, in the aggrecan/collagen II ratio, was found for healthy hips (p = 0.057) upon comparison of pressure areas (loaded areas > non-loaded areas). Moreover, compared with normal cartilage, OA cartilage showed a 10- to 20-fold lower ratio of aggrecan to type II collagen, suggesting that the balance between the major structural proteins is crucial to the integrity and function of the tissue. Alternatively, no differences in apoptosis levels between loading areas were found – evidence that mechanical load regulates cartilage matrix composition but does not affect chondrocyte viability. The results suggest that MMPs play a key role in regulating the balance of structural proteins of the articular cartilage matrix according to local mechanical demands. BioMed Central 2006 2006-09-14 /pmc/articles/PMC1779454/ /pubmed/16972994 http://dx.doi.org/10.1186/ar2042 Text en Copyright © 2006 Monfort et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Monfort, Jordi
Garcia-Giralt, Natalia
López-Armada, María J
Monllau, Joan C
Bonilla, Angeles
Benito, Pere
Blanco, Francisco J
Decreased metalloproteinase production as a response to mechanical pressure in human cartilage: a mechanism for homeostatic regulation
title Decreased metalloproteinase production as a response to mechanical pressure in human cartilage: a mechanism for homeostatic regulation
title_full Decreased metalloproteinase production as a response to mechanical pressure in human cartilage: a mechanism for homeostatic regulation
title_fullStr Decreased metalloproteinase production as a response to mechanical pressure in human cartilage: a mechanism for homeostatic regulation
title_full_unstemmed Decreased metalloproteinase production as a response to mechanical pressure in human cartilage: a mechanism for homeostatic regulation
title_short Decreased metalloproteinase production as a response to mechanical pressure in human cartilage: a mechanism for homeostatic regulation
title_sort decreased metalloproteinase production as a response to mechanical pressure in human cartilage: a mechanism for homeostatic regulation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1779454/
https://www.ncbi.nlm.nih.gov/pubmed/16972994
http://dx.doi.org/10.1186/ar2042
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