Development of an impingement induced, reversible degenerative meniscus tear animal model to analyze pathogenesis and potential recovery from meniscus degeneration.

OBJECTIVE

We aimed to develop a novel, impingement-induced, reversible degenerative meniscal tear (DMT) animal model to replicate the natural progression of meniscal degeneration and provide insights into the underlying mechanisms of DMTs in relation to osteoarthritis.

METHODS

A rabbit model was used to induce medial meniscal posterior horn (MMPH) impingement through anterior displacement. The animals were divided into degeneration and reversal groups, with reversal achieved through MMPH reduction. Histological analysis, MRI imaging, biomechanics, and gene expression assays were performed to assess the progression of meniscal degeneration.

RESULTS

MMPH impingement induced progressive, time-dependent meniscal degeneration, evidenced by histological, MRI, biomechanical, and molecular changes, with significantly worsening histological degeneration scores over time (D1wk-D8wk: Δ-9.00, 95%CI [-11.65, -6.35]). After reduction of the impinged MMPH, outcomes diverged according to the duration of prior impingement: reduction within 2 weeks was associated with attenuation of degeneration and no evidence of further progression, whereas reduction after 4 weeks was associated with continued structural deterioration despite removal of the impingement stimulus, reflected by worsening Pauli's scores (D8wk-R8wk: Δ-2.80, 95%CI [-5.10, -0.51]) and MRI grades (D8wk-R8wk: Δ-1.20, 95%CI [-2.02, -0.38]). This divergence between early and delayed reduction was consistently observed across biomechanical and molecular assessments, including reduced tensile modulus and ultimate tensile strength, decreased fibrogenic marker expression, and increased chondrogenic marker expression.

CONCLUSION

We have successfully developed an impingement-induced, reversible DMT animal model via anterior displacement of the MMPH, without the use of iatrogenic damage to MMPH with scalpels. Our model not only offers a DMT animal model that closely resembles human degenerative process without damage of other vital intra-articular structures, but also provides insight to the process of degeneration progression especially key tissue changes such as disruption in deep collagen fiber arrangement.