Early-stage knee OA induced by MIA and MMT compared in the murine model via histological and topographical approaches

Gaetan Aüllo-Rasser,Patrick Chabrand,Sandrine Roffino,Hassan Zahouani,Erick Dousset,Jean-Noël Argenson,Roger Lecurieux-Clerville

doi:10.1038/s41598-020-72350-7

Abstract

Osteoarthritis (OA) is a common degenerative disease whose early management includes promising mechanical treatments. New treatments are initially validated using an animal model in which OA is induced. The MMT (mechanical induction) and MIA (chemical induction) models of OA induction are widespread, but their use to generate early OA is poorly documented. We analyzed and compared early-stage knee OA-induction via these two methods in 16 rats divided into two groups. After 4 weeks of induction, the knees were sampled and studied using both histology (Toluidine Blue and Sirius Red) and surface topology, an innovative technique for characterizing osteoarthritic cartilage. The Mankin-modified score confirms that the two OA-induction models evolved at the same speed. At this early stage, the two models can be differentiated morphologically, although no significant differences were revealed by either cellularity or birefringence analysis. However, the topological analysis generated two forms of quantitative data, the deformation ratio and the cohesion index, that differentiated between the two groups. Thus, the early-stage OA induced by these two models is revealed to differ. The patterns of cartilage damage induced point to MMT as the better choice to assess mechanical approaches to clinical OA treatment.

Highlights

Osteoarthritis (OA) is a common degenerative disease whose early management includes promising mechanical treatments
OA management could open the way to treatments that focus on maintaining or even regenerating cartilage at a still-reversible stage of the pathology
Since the morphological analysis and Mankin score did not distinguish between healthy samples from the Medial Meniscal Transection (MMT) group and those from the MIA group, the healthy group consisted of 4 randomly selected samples

Summary

Introduction

Osteoarthritis (OA) is a common degenerative disease whose early management includes promising mechanical treatments. The MMT (mechanical induction) and MIA (chemical induction) models of OA induction are widespread, but their use to generate early OA is poorly documented. The Mankinmodified score confirms that the two OA-induction models evolved at the same speed At this early stage, the two models can be differentiated morphologically, no significant differences were revealed by either cellularity or birefringence analysis. OA management could open the way to treatments that focus on maintaining or even regenerating cartilage at a still-reversible stage of the pathology. Because the early stages of OA are asymptomatic, obtaining samples of human cartilage is difficult Such samples could not be used to study the potential therapeutic effects of a treatment, since the cartilage would be extracted from its environment. To the best of our knowledge, analysis has not yet been extended to early-stage OA

Objectives

Methods

Results

Discussion

Conclusion