Replication of chronic abnormal cartilage loading by medial meniscus destabilization for modeling osteoarthritis in the rabbit knee in vivo

Abstract

Medial meniscus destabilization (MMD) is a surgical insult technique for modeling osteoarthritis (OA) by replicating chronic abnormal cartilage loading in animal joints in vivo. The present study aimed to characterize the immediate biomechanical effects (ex vivo) and short-term histological consequences (in vivo) of MMD in the rabbit knee. In a compressive loading test, contact stress distribution in the medial compartment was measured in eight cadaver rabbit knees, initially with all major joint structures uninjured (Baseline), after MMD, and finally after total medial meniscectomy (TMM). Similarly, the effects on sagittal joint stability were determined in an anterior-posterior drawer test. These biomechanical (ex vivo) data indicated that both MMD and TMM caused significant (p < 0.001), distinct (>1.5-fold) elevation of peak local contact stress in the medial compartment, while leaving whole-joint stability nearly unchanged. Histological consequences in vivo were assessed in a short-term (8-week) survival series of MMD or TMM (five animals for each group), and both caused moderate cartilage degeneration in the medial compartment. The MMD insult, which is feasible through posterior arthrotomy alone, is as effective as TMM for modeling injurious-level chronic abnormal cartilage loading in the rabbit knee medial compartment in vivo, while minimizing potential confounding effects from whole-joint instability.

Keywords: contact stress; meniscus; post-traumatic osteoarthritis; rabbit knee; survival animal model.

Figure 1

A: Loading fixture for the axial compression test. B: Schematic of film position registration using fiducial markers; C: Determination of contact patch location in a strip of film (X = centroid of contact patch, C = coronal position, and S = sagittal position).

Figure 2

Left: Superior view of the rabbit knee tibial plateau with an intact medial meniscus (in a joint disarticulated for visualization). Right: Representative digitized Fujifilm images that indicate contact stress distribution in the medial compartment, for the three testing conditions in a joint. Approximate size of area covered by each contact patch image is illustrated as the dotted square on the tibial plateau photo. The corresponding numerical values for contact stress and contact area are indicated.

Figure 3

A: Custom loading fixture for the sagittal-plane laxity test. B: Definition of the neutral-zone length (NZL: displacement between ± 5 N) from the load-displacement relationship.

Figure 4

Biomechanical outcomes (ex vivo) from the cadaveric experimentation, in the axial compression test (A: contact area; B: peak contact stress; C: contact patch shift) and the sagittal-plane laxity tests (D) (n = 8, for all). The filled squares and dispersion bars indicate means and standard deviations. The X-plots in A, B, and D are individual specimens’ data. The coordinate origin of C is the contact patch centriod location for the Baseline condition.

Figure 5

Histological outcomes (in vivo) for each individual surface, from the survival series. Mankin scores for each individual animal are plotted, along with the mean values. The dispersion bars indicate standard deviations.