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 (5 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.

The Mechanobiology of Articular Cartilage: Bearing the Burden of Osteoarthritis

“…The two most common animal models of altered joint loading are ACL transection (ACLT), which causes increased joint laxity [69], and meniscal injury or meniscectomy, which alters cartilage contact pressure distributions [70]. Both of these models lead to degenerative joint changes similar to human joint injury [71, 72], and have been effective in identifying a number of disease-modifying enzymes, including ADAMTS5 [73], MMP-13 [74], and PAR-2 [75].…”

Kinematics of meniscal‐ and ACL‐transected mouse knees during controlled tibial compressive loading captured using roentgen stereophotogrammetry

“…[43][44][45]51 Thus, higher stresses occur in the cartilage, particularly over the medial aspect of the tibia. 17,50,52 Although both the ACLT and the DMM mouse models develop OA-like features, the results of this study, along with evidence from in vivo studies, suggest that the joint mechanical environment associated with disease initiation differ. The DMM model reflects increased contact stress due to a reduction of contact area.…”

“…Indeed, the progression of moderate OA in DMM and other meniscal injury situations has been attributed to the disruption of tibiofemoral contact mechanics, with damage to the meniscus causing decreased cartilage contact area . Thus, higher stresses occur in the cartilage, particularly over the medial aspect of the tibia . Although both the ACLT and the DMM mouse models develop OA‐like features, the results of this study, along with evidence from in vivo studies, suggest that the joint mechanical environment associated with disease initiation differ.…”

Animal Models of Meniscal Injury in Post-Traumatic Arthritis

“…The reparative tissue is wedge shaped and smaller than the normal meniscus, with some parallel collagen fi ber organization and mechanoreceptors present in the middle third [ 104 ]. Compared to DMM in rabbits, medial meniscectomy induced similar increases in contact area, lateral translocation of contact stress distribution, peak contract stress and Mankin scores in the medial joint compartment at 8 weeks postoperatively [ 64 ]. Following either medial meniscectomy or longitudinal tear in the rabbit, the sequence of OA development is the medial tibial plateau by 8 weeks, the posterior medial femoral condyle at 6-9 months, osteophyte development in 4-6 weeks.…”

“…DMM surgery in the rabbit has recently been described [ 64 ]. Peak contact stress in the medial compartment of operated joints was signifi cantly elevated immediately following DMM surgery.…”