Use of Contralateral Knee as Control in the Destabilization of Medial Meniscus Osteoarthritis Rat Model

Abstract

Destabilization of the medial meniscus (DMM) is a common surgical procedure used to induce osteoarthritis (OA) in a rodent model. However, there is a lack of evidence on using the contralateral limb as a control. Contralateral rat knees have been used as the control in noninvasive OA pain models, but not DMM models; and the contralateral limb of guinea pigs has been used to study the development of OA after DMM surgery. In a previous study, we examined the effects of DMM and obesity on the development and progression of OA in a rat model. In that study, 42 female Lewis rats were randomly assigned to 4 groups: Group 1 received a sham surgery (control) and was on a regular diet, Group 2 received a DMM surgery and was on a regular diet, Group 3 received a sham surgery and was on a high‐fat diet, and Group 4 received a DMM surgery and was on a high‐fat diet. The rats were on their respective diets for 4 weeks, underwent surgery, and were sacrificed 4 weeks after surgery. The knee joints of surgical and contralateral limbs were harvested. The Osteoarthritis Research Society International (OARSI) scoring system was used to score the damage to the articular cartilage of the knee. In the surgical limbs, DMM resulted in significantly greater OARSI scores than the sham surgery in the lateral and medial compartments of the knee in both diet groups. After that study, the contralateral knee tissues were stored in 10% formalin. For the current study, we used those stored tissues to determine whether the contralateral limbs could serve as a control in future studies that involve DMM in a rat model. Knees were decalcified, embedded in paraffin, and sectioned coronally at 10 μm. Slides were stained using Safranin O and fast green for counterstain. Four articular surfaces of the knee (medial and lateral femoral condyles and medial and lateral tibial plateaus) were histologically evaluated for degenerative changes by a blinded scorer. A generalized linear mixed model was used to analyze differences between the rat knee groups. Comparison of sham and DMM rat knees across both diet groups showed no significant difference in OARSI scores (P=.61). When comparing within each of the diet groups, there was no significant difference between the DMM and sham scores in the high‐fat diet groups (P>.99) or regular diet groups (P=.49). After comparing the knee surface scores for all groups, the medial tibial plateau had significantly lower scores than the other 3 surfaces (P<.001). Based on results of the current study, we believe the contralateral limb can be used as a control in short‐term (4 weeks or less) OA studies using DMM in a rat model. This will save time and resources by achieving an adequate sample size with fewer animals. Our results also showed that the medial tibial plateau was significantly less susceptible to the development of spontaneous OA compared to the other 3 articular surfaces studied.Support or Funding InformationSupport for this project was received from Dr. Peter Kondrashov, Department of Anatomy, A.T. Still University, Kirksville College of Osteopathic Medicine.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.