Spontaneous osteoarthritis in Str/ort mice is unlikely due to greater vulnerability to mechanical trauma

B Poulet,T.A.T Westerhof,R.W Hamilton,S.J Shefelbine,A.A Pitsillides

doi:10.1016/j.joca.2013.02.652

B Poulet, T.A.T Westerhof + Show 3 more

Open Access

https://doi.org/10.1016/j.joca.2013.02.652

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Abstract

Relative contributions of genetic and mechanical factors to osteoarthritis (OA) remain ill-defined. We have used a joint loading model found to produce focal articular cartilage (AC) lesions, to address whether genetic susceptibility to OA in Str/ort mice is related to AC vulnerability to mechanical trauma and whether joint loading influences spontaneous OA development. We also develop finite element (FE) models to examine whether AC thickness may explain any differential vulnerability to load-induced lesions. Right knees of 8-week-old Str/ort mice were loaded, AC integrity scored and thickness compared to CBA mice. Mechanical forces engendered in this model and the impact of AC thickness were simulated in C57Bl/6 mice using quasi-static FE modelling. Unlike joints in non-OA prone CBA mice, Str/ort knees did not exhibit lateral femur (LF) lesions in response to applied loading; but exhibited thicker AC. FE modeling showed increased contact pressure and shear on the lateral femoral surface in loaded joints, and these diminished in joints containing thicker AC. Histological analysis of natural lesions in the tibia of Str/ort joints revealed that applied loading increased OA severity, proteoglycan loss and collagen type II degradation. Genetic OA susceptibility in Str/ort mice is not apparently related to greater AC vulnerability to trauma, but joint loading modifies severity of natural OA lesions in the medial tibia. FE modelling suggests that thicker AC in Str/ort mice diminishes tissue stresses and protects against load-induced AC lesions in the LF but that this is unrelated to their genetic susceptibility to OA.

Highlights

Osteoarthritis (OA) is a complex disease with major genetic and mechanical contributions[1,2]
We found that 8-week-old Str/ort mice did not develop significant lateral femur (LF) lesions following 2 weeks of applied loading (Fig. 2; n 1⁄4 8) and that, similar to other strains[12], load-induced lesions were lacking in the lateral tibia and medial femur compartments
We find using novel finite element (FE) modeling of mouse knee joints during loading that increased articular cartilage (AC) thickness may account for this relative protection against loadinduced AC lesions

Summary

Introduction

Osteoarthritis (OA) is a complex disease with major genetic and mechanical contributions[1,2]. Genetic contributions to human OA exhibit Mendelian transmission[2,4], and highlight a contribution from environmental, predominantly mechanical factors5e7. These contributions might depend upon the extent to which each gene product interacts with joint mechanics, and upon which specific mechanical factors promote OA. It is known, for instance, that jogging does not modify OA risk[5], but that squatting, heavy lifting and repetitive, high impact/intensity sports are strongly associated[6,7]

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