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

Ramos-Mucci, Lorenzo ORCID: 0000-0003-4346-8861, Elsheikh, Ahmed ORCID: 0000-0001-7456-1749, Keenan, Craig ORCID: 0000-0002-8782-8016, Eliasy, Ashkan ORCID: 0000-0002-4473-1900, D’Aout, Kris, Bou-Gharios, George, Comerford, Eithne ORCID: 0000-0002-5244-6042 and Poulet, Blandine
(2021) The anterior cruciate ligament in murine post-traumatic osteoarthritis: markers and mechanics. [Preprint]

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1 Osteoarthritis (OA) is a whole joint disease that affects all knee joint tissues. Ligaments, a matrix-rich connective tissue, play an important mechanical function that stabilises the knee joint and yet their role in OA is not well studied. Recent studies have shown that ligament extracellular matrix (ECM) structure is compromised in the early stages of OA, but it remains unclear how this affects ligament function and biomechanics. In this study, the aim was to investigate the structural, cellular and viscoelastic changes in the anterior cruciate ligament (ACL) in a murine non-invasive post-traumatic OA (PTOA) model. Non-invasive mechanical loading of the knee joint of C57BL/6J mice (10-week-old) was used as a PTOA model. Knee joints were analysed for joint space mineralisation and the ACLs were assessed with histology and mechanical testing. PTOA knee joints had a 33-46% increase in joint space mineralisation and PTOA knee joint ACLs exhibited ECM modifications, including collagen birefringence and COL2 and proteoglycan deposition. ECM changes were associated with cells expressing chondrogenic markers (SOX9 and RUNX2) expanding from the tibial enthesis to the ACL midbody. Viscoelastic and mechanical changes in the ACLs from PTOA knee joints included a 20-21% decrease in tangent modulus at 2MPa of stress, and a decrease strain rate sensitivity at higher strain rates and a significant increase in relaxation during stress-relaxation, but no changes to hysteresis and ultimate load to failure. These results demonstrate that ACL pathology and viscoelastic function is compromised in murine PTOA knee joints and provides further evidence of the important role of ligaments in the knee joint organ in health and disease.

Item Type: Preprint
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences
Faculty of Science and Engineering > School of Engineering
Depositing User: Symplectic Admin
Date Deposited: 15 Nov 2021 07:57
Last Modified: 18 Jan 2023 21:24
DOI: 10.1101/2021.11.08.467455
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