Nano-Scale Mechanical Properties of the Articular Cartilage Zones in a Mouse Model of Post-Traumatic Osteoarthritis

Lutz Fleischhauer,Zsuzsanna Farkas,Dominique Muschter,Attila Aszodi,Susanne Grässel,Paolo Alberton,Hauke Clausen-Schaumann

doi:10.3390/app12052596

Abstract

Destabilization of the medial meniscus (DMM) surgery in mice is used to elucidate the mechanism of post-traumatic osteoarthritis (PT-OA). The study of cartilage biomechanics in PT-OA is important for understanding the pathophysiology of the condition. We used indentation-type atomic force microscopy (IT-AFM) to assess the nanostiffness of the interterritorial matrix of articular cartilage (AC) zones in the medial and the lateral tibia plateau (MTP and LTP) on native tissue sections 2 and 8 weeks after DMM or Sham surgery. At 2 weeks, pronounced stiffening of the DMM AC was observed compared to Sham, with the most marked changes occurring in the superficial zone and affecting the proteoglycan moiety rather than the collagen network. The LTP cartilage was obviously stiffer than the MTP in DMM, but not in Sham. At 8 weeks, only modest differences in nanostiffness were observed between DMM and Sham. The difference in stiffness between MTP and LTP was reduced, and the proteoglycan and collagen phases changed in a more similar manner. Interestingly, the deep zone was softer in the DMM compared to the Sham. Sham AC showed an increase in stiffness between 2 and 8 weeks, a trend that was counteracted in the DMM group. Collectively, our study demonstrates that nano-scale IT-AFM is a sensitive tool to monitor biomechanical changes during the course of PT-OA.

Highlights

Osteoarthritis (OA) is the leading musculoskeletal disease worldwide, and is characterized by a complex and multifactorial etiology [1,2]
Eiggrhotuwp,siumrpgleicrayt,infogcoanllyabasmenilcdeporfogSraefsrsaionnino-fOOsAt.aTinhiensgiginnidfiiccaanttilvyedifferent of proteoglycan losMs awnaksinosbcsoerrevs eind tihnetmheedMiaTl PtiboifalDcMomMpamrtmiceen(tFriegmuraein1eAd,bwetwhieteenatrhreowSh)abmu-tand the articular cartilage (AC) degradation scDoMreMs -wopeerreatoendlgyrosulipg(h2t.0ly0 ±el0e.v00atveedrsucos m5.6p7a±re1d.70t,opt=h0e.0238w);eheokwsevpeors, wt-oe ponelryao-bserved a tendency of higher Mankin scores for MTP compared to LTP in Destabilization of the medial meniscus (DMM) mice, which did tion group (Figure 1B), implicating only a mild progression of OA
The significantly different Mankin scores in the medial tibial compartment remained between the Sham- and the DMM-operated group (2.00 ± 0.00 versus 5.67 ± 1.70, p = 0.038); we only observed a tendency of higher Mankin scores for MTP compared to LTP in DMM mice, not reach the level of significance

Summary

Introduction

Osteoarthritis (OA) is the leading musculoskeletal disease worldwide, and is characterized by a complex and multifactorial etiology [1,2]. High-risk factors affecting the onset and progression of OA include increasing age, obesity and/or metabolic conditions, joint overuse and injuries of the musculoskeletal system [4]. All these factors may lead to altered biomechanical loading, which progressively contributes to the imbalance of cartilage homeostasis, eventually resulting in AC degeneration and OA. No cure or disease-modifying drug is available for OA and therapeutic interventions aim to relieve symptoms or eliminate the problem via joint replacement [5].

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