Comparison between two rabbit models of posttraumatic osteoarthritis: A longitudinal tear in the medial meniscus and anterior cruciate ligament transection

Abstract

Animal osteoarthritis (OA) models have been developed to understand OA progression and evaluate new OA therapies. However, individual variations in joint lesions remain a critical problem in most current OA models. We established a novel rabbit model by creating a longitudinal tear in the medial meniscus body that was reproducible and similar to posttraumatic biomechanical disturbances in human OA. New Zealand rabbits underwent surgery and were assessed for 9 weeks. The rabbits were randomized into the sham control, medial meniscal tear (MMT), and anterior cruciate ligament transection (ACLT) groups. The animals were sacrificed at 4, 6, and 9 weeks posttreatment. The knee joints were harvested for histological and gene expression assessments. Both the MMT and ACLT procedures led to time‐dependent degenerative changes in the femoral condyle cartilage. At each time point, the MMT group cartilage showed more severe degenerative changes than did the ACLT group cartilage. Consistently, inflammatory cytokine and catabolic gene expression were significantly higher, and anabolic gene expression was significantly lower in the MMT group than in the ACLT group. MMT treatment caused more severe structural damage to the cartilage and higher catabolic gene expression levels than the ACLT model at each time point. The MMT model may be highly beneficial in investigating posttraumatic OA (PTOA) development, especially PTOA from a meniscal injury. The MMT model replicated key features of human PTOA, including meniscal lesions, inflammatory responses, and the progression to osteoarthritic cartilage degeneration, thereby providing an exciting new avenue for translating promising treatments to clinical practice.

Post-traumatic osteoarthritis: A review of pathogenic mechanisms and novel targets for mitigation

“…Increased inflammation also correlates with enhanced catabolic and inflammatory marker expression by chondrocytes ( Fig. 2 ) ( Heard et al, 2011 ; Huang et al, 2020 ; Han et al, 2018 ). Corticosteroids, such as dexamethasone, have been shown to mitigate the inflammatory response to TNF-α and IL-6, while decreasing GAG loss in cartilage and increasing proteoglycan synthesis ( Lu et al, 2011 ).…”

“…Aberrant loading of the joint surface is associated with elevated levels of inflammatory markers such as IL-1β and IL-6 released by synoviocytes and chondrocytes into the joint microenvironment and their downstream mediators such as inducible nitric oxide synthase (iNOS) and NO ( He et al, 2018 ; Abramson, 2008 ). This is coupled with decreased expression of markers of cartilage anabolism (type II collagen (COL2), aggrecan), and increased levels of markers of cartilage catabolism (ADAMTS-4, ADAMTS-5, MMP-13, MMP-3) in chondrocytes ( Liu et al, 2016 ; Huang et al, 2020 ) ( Table 2 ). Even after the restoration of joint biomechanics through surgical restoration of joint stability, such as ACL reconstruction, MMP-13 levels remain elevated for a prolonged period.…”

Evaluation of the Anti-inflammatory Effect of Intra-articular Injection of Chondroitin Sulfate and Sodium Hyaluronate in Mechanically Induced Temporomandibular Joint Injury in Rabbits

“…The experimental study was based on 32 male rabbits that were subjected to induction of osteochondral defect, we were investigating the effect of intra-articular injection of sodium hyaluronate + chondroitin sulfate on inflammatory reaction and cartilage formation on the defect, through histopathological observation. Many osteoarthritic animal models used surgical approaches to initiate joint degeneration, and each method is designed to study a specific aspect of the injury or subsequent disease development, the present experimental study design was in accordance with multiple researches in terms of creating mechanical osteochondral defect in animals, either in dogs [11], sheep [15], or in rabbits [13], [16], [17], [18] as in this case, we selected New Zealand rabbits for being an easily available and less aggressive animals [19], [20], although the horse articular cartilage is the most comparable to humans, and they have been used to study articular cartilage repair and osteochondral defects [21], [22], yet rabbits remain easier for manipulation and have affordable cost.…”