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

Lorenzo Ramos-Mucci, Ahmed Elsheikh, Craig Keenan, Ashkan Eliasy, Kristiaan D’Aout, George Bou-Gharios, Eithne Comerford, Blandine Poulet*

*Corresponding author for this work

Research output: Contribution to journalArticle (journal)peer-review

Abstract

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.

Original languageEnglish
Article number128
JournalArthritis Research and Therapy
Volume24
Issue number1
Early online date30 May 2022
DOIs
Publication statusE-pub ahead of print - 30 May 2022

Keywords

  • Anterior cruciate ligament
  • Chondrogenesis
  • Mechanics
  • Post-traumatic osteoarthritis
  • Viscoelastic

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