Obesity alters the collagen organization and mechanical properties of murine cartilage

Amber T Collins,Deepika Sharma,Leyao Shen,Holly A Leddy,Monique R Goldsmith,John N Twomey-Kozak,Michael H Reinsvold,Hunter Newman,Louis E Defrate,Guoli Hu,Courtney M Karner

doi:10.1038/s41598-020-80599-1

Abstract

Osteoarthritis is a debilitating disease characterized by cartilage degradation and altered cartilage mechanical properties. Furthermore, it is well established that obesity is a primary risk factor for osteoarthritis. The purpose of this study was to investigate the influence of obesity on the mechanical properties of murine knee cartilage. Two-month old wild type mice were fed either a normal diet or a high fat diet for 16 weeks. Atomic force microscopy-based nanoindentation was used to quantify the effective indentation modulus of medial femoral condyle cartilage. Osteoarthritis progression was graded using the OARSI system. Additionally, collagen organization was evaluated with picrosirius red staining imaged using polarized light microscopy. Significant differences between diet groups were assessed using t tests with p < 0.05. Following 16 weeks of a high fat diet, no significant differences in OARSI scoring were detected. However, we detected a significant difference in the effective indentation modulus between diet groups. The reduction in cartilage stiffness is likely the result of disrupted collagen organization in the superficial zone, as indicated by altered birefringence on polarized light microscopy. Collectively, these results suggest obesity is associated with changes in knee cartilage mechanical properties, which may be an early indicator of disease progression.

Highlights

Osteoarthritis is a debilitating disease characterized by cartilage degradation and altered cartilage mechanical properties
Our results show that obese mice had decreased cartilage stiffness coincident with disruption of collagen organization in the superficial zone
In order to examine the effects of obesity on cartilage health, we utilized the diet-induced obesity (DIO) mouse model

Summary

Introduction

Osteoarthritis is a debilitating disease characterized by cartilage degradation and altered cartilage mechanical properties. The purpose of this study was to investigate the influence of obesity on the mechanical properties of murine knee cartilage. The reduction in cartilage stiffness is likely the result of disrupted collagen organization in the superficial zone, as indicated by altered birefringence on polarized light microscopy These results suggest obesity is associated with changes in knee cartilage mechanical properties, which may be an early indicator of disease progression. Because it is difficult to directly evaluate cartilage mechanical properties in vivo, it is unclear whether these increased strains are due to elevated joint loading, decreased cartilage stiffness, or a combination of both. As an alternative to in vivo testing, diet-induced obese mouse models have been used to study OA pathogenesis[17,18,19,20] primarily due to their accelerated OA onset and progression. Atomic force microscopy (AFM) can be used to evaluate the mechanical properties of murine cartilage tissue[21,22,23,24]

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