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An in silico Framework of Cartilage Degeneration That Integrates Fibril Reorientation and Degradation Along With Altered Hydration and Fixed Charge Density Loss
Injurious mechanical loading of articular cartilage and associated lesions compromise the mechanical and structural integrity of joints and contribute to the onset and progression of cartilage degeneration leading to osteoarthritis (OA). Despite extensive in vitro and in vivo research, it remains un...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258121/ https://www.ncbi.nlm.nih.gov/pubmed/34239859 http://dx.doi.org/10.3389/fbioe.2021.680257 |
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author | Elahi, Seyed Ali Tanska, Petri Korhonen, Rami K. Lories, Rik Famaey, Nele Jonkers, Ilse |
author_facet | Elahi, Seyed Ali Tanska, Petri Korhonen, Rami K. Lories, Rik Famaey, Nele Jonkers, Ilse |
author_sort | Elahi, Seyed Ali |
collection | PubMed |
description | Injurious mechanical loading of articular cartilage and associated lesions compromise the mechanical and structural integrity of joints and contribute to the onset and progression of cartilage degeneration leading to osteoarthritis (OA). Despite extensive in vitro and in vivo research, it remains unclear how the changes in cartilage composition and structure that occur during cartilage degeneration after injury, interact. Recently, in silico techniques provide a unique integrated platform to investigate the causal mechanisms by which the local mechanical environment of injured cartilage drives cartilage degeneration. Here, we introduce a novel integrated Cartilage Adaptive REorientation Degeneration (CARED) algorithm to predict the interaction between degenerative variations in main cartilage constituents, namely collagen fibril disorganization and degradation, proteoglycan (PG) loss, and change in water content. The algorithm iteratively interacts with a finite element (FE) model of a cartilage explant, with and without variable depth to full-thickness defects. In these FE models, intact and injured explants were subjected to normal (2 MPa unconfined compression in 0.1 s) and injurious mechanical loading (4 MPa unconfined compression in 0.1 s). Depending on the mechanical response of the FE model, the collagen fibril orientation and density, PG and water content were iteratively updated. In the CARED model, fixed charge density (FCD) loss and increased water content were related to decrease in PG content. Our model predictions were consistent with earlier experimental studies. In the intact explant model, minimal degenerative changes were observed under normal loading, while the injurious loading caused a reorientation of collagen fibrils toward the direction perpendicular to the surface, intense collagen degradation at the surface, and intense PG loss in the superficial and middle zones. In the injured explant models, normal loading induced intense collagen degradation, collagen reorientation, and PG depletion both on the surface and around the lesion. Our results confirm that the cartilage lesion depth is a crucial parameter affecting tissue degeneration, even under physiological loading conditions. The results suggest that potential fibril reorientation might prevent or slow down fibril degradation under conditions in which the tissue mechanical homeostasis is perturbed like the presence of defects or injurious loading. |
format | Online Article Text |
id | pubmed-8258121 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-82581212021-07-07 An in silico Framework of Cartilage Degeneration That Integrates Fibril Reorientation and Degradation Along With Altered Hydration and Fixed Charge Density Loss Elahi, Seyed Ali Tanska, Petri Korhonen, Rami K. Lories, Rik Famaey, Nele Jonkers, Ilse Front Bioeng Biotechnol Bioengineering and Biotechnology Injurious mechanical loading of articular cartilage and associated lesions compromise the mechanical and structural integrity of joints and contribute to the onset and progression of cartilage degeneration leading to osteoarthritis (OA). Despite extensive in vitro and in vivo research, it remains unclear how the changes in cartilage composition and structure that occur during cartilage degeneration after injury, interact. Recently, in silico techniques provide a unique integrated platform to investigate the causal mechanisms by which the local mechanical environment of injured cartilage drives cartilage degeneration. Here, we introduce a novel integrated Cartilage Adaptive REorientation Degeneration (CARED) algorithm to predict the interaction between degenerative variations in main cartilage constituents, namely collagen fibril disorganization and degradation, proteoglycan (PG) loss, and change in water content. The algorithm iteratively interacts with a finite element (FE) model of a cartilage explant, with and without variable depth to full-thickness defects. In these FE models, intact and injured explants were subjected to normal (2 MPa unconfined compression in 0.1 s) and injurious mechanical loading (4 MPa unconfined compression in 0.1 s). Depending on the mechanical response of the FE model, the collagen fibril orientation and density, PG and water content were iteratively updated. In the CARED model, fixed charge density (FCD) loss and increased water content were related to decrease in PG content. Our model predictions were consistent with earlier experimental studies. In the intact explant model, minimal degenerative changes were observed under normal loading, while the injurious loading caused a reorientation of collagen fibrils toward the direction perpendicular to the surface, intense collagen degradation at the surface, and intense PG loss in the superficial and middle zones. In the injured explant models, normal loading induced intense collagen degradation, collagen reorientation, and PG depletion both on the surface and around the lesion. Our results confirm that the cartilage lesion depth is a crucial parameter affecting tissue degeneration, even under physiological loading conditions. The results suggest that potential fibril reorientation might prevent or slow down fibril degradation under conditions in which the tissue mechanical homeostasis is perturbed like the presence of defects or injurious loading. Frontiers Media S.A. 2021-06-22 /pmc/articles/PMC8258121/ /pubmed/34239859 http://dx.doi.org/10.3389/fbioe.2021.680257 Text en Copyright © 2021 Elahi, Tanska, Korhonen, Lories, Famaey and Jonkers. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Bioengineering and Biotechnology Elahi, Seyed Ali Tanska, Petri Korhonen, Rami K. Lories, Rik Famaey, Nele Jonkers, Ilse An in silico Framework of Cartilage Degeneration That Integrates Fibril Reorientation and Degradation Along With Altered Hydration and Fixed Charge Density Loss |
title | An in silico Framework of Cartilage Degeneration That Integrates Fibril Reorientation and Degradation Along With Altered Hydration and Fixed Charge Density Loss |
title_full | An in silico Framework of Cartilage Degeneration That Integrates Fibril Reorientation and Degradation Along With Altered Hydration and Fixed Charge Density Loss |
title_fullStr | An in silico Framework of Cartilage Degeneration That Integrates Fibril Reorientation and Degradation Along With Altered Hydration and Fixed Charge Density Loss |
title_full_unstemmed | An in silico Framework of Cartilage Degeneration That Integrates Fibril Reorientation and Degradation Along With Altered Hydration and Fixed Charge Density Loss |
title_short | An in silico Framework of Cartilage Degeneration That Integrates Fibril Reorientation and Degradation Along With Altered Hydration and Fixed Charge Density Loss |
title_sort | in silico framework of cartilage degeneration that integrates fibril reorientation and degradation along with altered hydration and fixed charge density loss |
topic | Bioengineering and Biotechnology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258121/ https://www.ncbi.nlm.nih.gov/pubmed/34239859 http://dx.doi.org/10.3389/fbioe.2021.680257 |
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