Dataset Information

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

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.

SUBMITTER: Ramos-Mucci L

PROVIDER: S-EPMC9150328 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Publications

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

Ramos-Mucci Lorenzo L Elsheikh Ahmed A Keenan Craig C Eliasy Ashkan A D'Aout Kristiaan K Bou-Gharios George G Comerford Eithne E Poulet Blandine B

Arthritis research & therapy 20220530 1

<h4>Background</h4>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 li ...[more]

PMID: 35637500

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Project description:BackgroundAnterior cruciate ligament (ACL) ruptures are a potent risk factor for post-traumatic knee osteoarthritis (PTOA). Annually, in Aotearoa New Zealand, approximately 2,500 people under the age of 30 undergo ACL reconstruction surgery. Due to the young age of injury and surgery, many develop osteoarthritis before age 50 and have a higher likelihood of requiring total knee replacement compared to the general population. This study aimed to gain insight into the medium- to long-term impacts of ACL rupture on people's well-being in Aotearoa New Zealand, by exploring their lived experiences five or more years post-injury.MethodIn this Interpretive Description observational study, we conducted semi-structured interviews with people who had ruptured their ACL and had or were at risk of developing PTOA. Analysis was conducted guided by Braun and Clarke's Reflexive Thematic Analysis.FindingsTwelve people (7 women, median age 49.5 [25-62] years) were interviewed. Three themes were generated from the data: 1) Nobody Ever Told Me…, 2) The Post-Rehabilitation Void, and 3) The Elephant in the Room: The Psychosocial Impact. Participants commonly described fear, grief and long-term psychological impacts, and most reported wanting to know more about the long-term management of their knees.Conclusion and impactThe study highlights opportunities to provide better long-term support and management, improve outcomes, and reduce the burden on these individuals. ACL injury can profoundly impact people's lives in the long term. Better education, support services, and consideration of psychosocial factors are needed. Addressing identified barriers could reduce the individual and socioeconomic burden of PTOA for New Zealanders. Future research involving stakeholders must establish acceptable long-term management programmes tailored to ensure they meet the population's needs and address the unique socioeconomic context and ethnic disparities in Aotearoa New Zealand.

Project description:Joint injury is the predominant risk factor for post-traumatic osteoarthritis development (PTOA). Several non-invasive mouse models mimicking human PTOA investigate molecular mechanisms of disease development; none have characterized the inflammatory response to this acute traumatic injury. Our aim was to characterize the early inflammatory phase and later degenerative component in our in vivo non-invasive murine model of PTOA induced by anterior cruciate ligament (ACL) rupture. Right knees of 12-week-old C57Bl6 mice were placed in flexion at a 30° offset position and subjected to a single compressive load (12N, 1.4 mm/s) to induce ACL rupture with no obvious damage to surrounding tissues. Tissue was harvested 4 h post-injury and on days 3, 14, and 21; contralateral left knees served as controls. Histological, immunohistochemical, and gene analyzes were performed to evaluate inflammatory and degenerative changes. Immunohistochemistry revealed time-dependent expression of mature (F4/80 positive) and inflammatory (CD11b positive) macrophage populations within the sub-synovial infiltrate, developing osteophytes, and inflammation surrounding the ACL in response to injury. Up-regulation of genes encoding acute pro-inflammatory markers, inducible nitric oxide synthase, interleukin-6 and interleukin-17, and the matrix degrading enzymes, ADAMTS-4 and MMP3 was detected in femoral cartilage, concomitant with extensive cartilage damage and bone remodelling over 21-days post-injury. Our non-invasive model describes pathologically distinct phases of the disease, increasing our understanding of inflammatory episodes, the tissues/cells producing inflammatory mediators and the early molecular changes in the joint, thereby defining the early phenotype of PTOA. This knowledge will guide appropriate interventions to delay or arrest disease progression following joint injury. © 2018 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals, Inc. on behalf of the Orthopaedic Research Society. J Orthop Res 9999:1-10, 2018.

Project description:BackgroundWe aimed to evaluate clinical and radiological results after simultaneous open-wedge high tibial osteotomy (HTO) and anterior cruciate ligament (ACL) reconstruction in patients with ACL deficiency combined with medial uni-compartmental osteoarthritis (OA) and varus deformity.MethodsThis retrospective study was performed using data collected from 2005 to 2011 on a total of 24 patients who were diagnosed with ACL injury and medial unicompartmental OA with varus deformity, and who subsequently underwent simultaneous open-wedge HTO and arthroscopic ACL reconstruction. The mean follow-up duration was 5.2 years. For clinical outcomes, we evaluated Lysholm score, Tegner activity score, range of motion, Lachmann test, and pivot-shift test, and for radiological outcomes, we evaluated the degree of varus deformity, progression of medial OA, tibial posterior slope, anterior instability, and postoperative complication.ResultsThere were no limitations in range of motion found in any cases. Three patients showed progressive osteoarthritis on the medial compartment. The mechanical femorotibial angle was significantly corrected from varus 7.0 degrees to valgus 1.2 degrees, and the tibial posterior slope was not significantly changed. The Lysholm and Tegner activity scores were significantly improved after surgery (from 58 to 94 points on the Lysholm scale and from 4.0 to 5.3 points on the Tegner activity scale). Although the Lachman test and the pivot-shift test showed significant improvements after surgery, instability greater than Gr II was observed in three patients on the Lachman test and in four patients on the pivot-shift test. The side-to-side difference improved from 9.6 mm to 4.2 mm postoperatively as assessed using a Telos® arthrometer. There were no cases of nonunion or fixation loss.ConclusionsSimultaneous open-wedge HTO and ACL reconstruction in patients with ACL injury with medial compartmental OA showed satisfactory functional outcomes and postoperative activity level scores. However, some patients showed residual instability and progression of OA.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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