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The anterior cruciate ligament in murine post-traumatic osteoarthritis: markers and mechanics

BACKGROUND: Knee joint injuries, common in athletes, have a high risk of developing post-traumatic osteoarthritis (PTOA). Ligaments, matrix-rich connective tissues, play important mechanical functions stabilising the knee joint, and yet their role post-trauma is not understood. Recent studies have s...

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Autores principales: Ramos-Mucci, Lorenzo, Elsheikh, Ahmed, Keenan, Craig, Eliasy, Ashkan, D’Aout, Kristiaan, Bou-Gharios, George, Comerford, Eithne, Poulet, Blandine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9150328/
https://www.ncbi.nlm.nih.gov/pubmed/35637500
http://dx.doi.org/10.1186/s13075-022-02798-7
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author Ramos-Mucci, Lorenzo
Elsheikh, Ahmed
Keenan, Craig
Eliasy, Ashkan
D’Aout, Kristiaan
Bou-Gharios, George
Comerford, Eithne
Poulet, Blandine
author_facet Ramos-Mucci, Lorenzo
Elsheikh, Ahmed
Keenan, Craig
Eliasy, Ashkan
D’Aout, Kristiaan
Bou-Gharios, George
Comerford, Eithne
Poulet, Blandine
author_sort Ramos-Mucci, Lorenzo
collection PubMed
description BACKGROUND: Knee joint injuries, common in athletes, have a high risk of developing post-traumatic osteoarthritis (PTOA). Ligaments, matrix-rich connective tissues, play important mechanical functions stabilising the knee joint, and yet their role post-trauma is not understood. Recent studies have shown that ligament extracellular matrix structure is compromised in the early stages of spontaneous osteoarthritis (OA) and PTOA, but it remains unclear how ligament matrix pathology affects ligament mechanical function. In this study, we aim to investigate both structural and mechanical changes in the anterior cruciate ligament (ACL) in a mouse model of knee trauma. METHODS: Knee joints were analysed following non-invasive mechanical loading in male C57BL/6 J mice (10-week-old). Knee joints were analysed for joint space mineralisation to evaluate OA progression, and the ACLs were assessed with histology and mechanical testing. RESULTS: Joints with PTOA had a 33–46% increase in joint space mineralisation, indicating OA progression. Post-trauma ACLs exhibited extracellular matrix modifications, including COL2 and proteoglycan deposition. Additional changes included cells expressing chondrogenic markers (SOX9 and RUNX2) expanding from the ACL tibial enthesis to the mid-substance. Viscoelastic and mechanical changes in the ACLs from post-trauma knee joints included a 20–21% decrease in tangent modulus at 2 MPa of stress, a decrease in strain rate sensitivity at higher strain rates and an increase in relaxation during stress-relaxation, but no changes to hysteresis and ultimate load to failure were observed. CONCLUSIONS: These results demonstrate that ACL pathology and viscoelastic function are compromised in the post-trauma knee joint and reveal an important role of viscoelastic mechanical properties for ligament and potentially knee joint health. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13075-022-02798-7.
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spelling pubmed-91503282022-05-31 The anterior cruciate ligament in murine post-traumatic osteoarthritis: markers and mechanics Ramos-Mucci, Lorenzo Elsheikh, Ahmed Keenan, Craig Eliasy, Ashkan D’Aout, Kristiaan Bou-Gharios, George Comerford, Eithne Poulet, Blandine Arthritis Res Ther Research BACKGROUND: Knee joint injuries, common in athletes, have a high risk of developing post-traumatic osteoarthritis (PTOA). Ligaments, matrix-rich connective tissues, play important mechanical functions stabilising the knee joint, and yet their role post-trauma is not understood. Recent studies have shown that ligament extracellular matrix structure is compromised in the early stages of spontaneous osteoarthritis (OA) and PTOA, but it remains unclear how ligament matrix pathology affects ligament mechanical function. In this study, we aim to investigate both structural and mechanical changes in the anterior cruciate ligament (ACL) in a mouse model of knee trauma. METHODS: Knee joints were analysed following non-invasive mechanical loading in male C57BL/6 J mice (10-week-old). Knee joints were analysed for joint space mineralisation to evaluate OA progression, and the ACLs were assessed with histology and mechanical testing. RESULTS: Joints with PTOA had a 33–46% increase in joint space mineralisation, indicating OA progression. Post-trauma ACLs exhibited extracellular matrix modifications, including COL2 and proteoglycan deposition. Additional changes included cells expressing chondrogenic markers (SOX9 and RUNX2) expanding from the ACL tibial enthesis to the mid-substance. Viscoelastic and mechanical changes in the ACLs from post-trauma knee joints included a 20–21% decrease in tangent modulus at 2 MPa of stress, a decrease in strain rate sensitivity at higher strain rates and an increase in relaxation during stress-relaxation, but no changes to hysteresis and ultimate load to failure were observed. CONCLUSIONS: These results demonstrate that ACL pathology and viscoelastic function are compromised in the post-trauma knee joint and reveal an important role of viscoelastic mechanical properties for ligament and potentially knee joint health. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13075-022-02798-7. BioMed Central 2022-05-30 2022 /pmc/articles/PMC9150328/ /pubmed/35637500 http://dx.doi.org/10.1186/s13075-022-02798-7 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Ramos-Mucci, Lorenzo
Elsheikh, Ahmed
Keenan, Craig
Eliasy, Ashkan
D’Aout, Kristiaan
Bou-Gharios, George
Comerford, Eithne
Poulet, Blandine
The anterior cruciate ligament in murine post-traumatic osteoarthritis: markers and mechanics
title The anterior cruciate ligament in murine post-traumatic osteoarthritis: markers and mechanics
title_full The anterior cruciate ligament in murine post-traumatic osteoarthritis: markers and mechanics
title_fullStr The anterior cruciate ligament in murine post-traumatic osteoarthritis: markers and mechanics
title_full_unstemmed The anterior cruciate ligament in murine post-traumatic osteoarthritis: markers and mechanics
title_short The anterior cruciate ligament in murine post-traumatic osteoarthritis: markers and mechanics
title_sort anterior cruciate ligament in murine post-traumatic osteoarthritis: markers and mechanics
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9150328/
https://www.ncbi.nlm.nih.gov/pubmed/35637500
http://dx.doi.org/10.1186/s13075-022-02798-7
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