Extracellular matrix integrity affects the mechanical behaviour of in-situ chondrocytes under compression.
Cartilage lesions change the microenvironment of cells and may accelerate cartilage degradation through catabolic responses from chondrocytes. In this study, we investigated the effects of structural integrity of the extracellular matrix (ECM) on chondrocytes by comparing the mechanics of cells surrounded by an intact ECM with cells close to a cartilage lesion using experimental and numerical methods. Experimentally, 15% nominal compression was applied to bovine cartilage tissues using a light-transmissible compression system. Target cells in the intact ECM and near lesions were imaged by dual-photon microscopy. Changes in cell morphology (N(cell)=32 for both ECM conditions) were quantified. A two-scale (tissue level and cell level) Finite Element (FE) model was also developed. A 15% nominal compression was applied to a non-linear, biphasic tissue model with the corresponding cell level models studied at different radial locations from the centre of the sample in the transient phase and at steady state. We studied the Green-Lagrange strains in the tissue and cells. Experimental and theoretical results indicated that cells near lesions deform less axially than chondrocytes in the intact ECM at steady state. However, cells near lesions experienced large tensile strains in the principal height direction, which are likely associated with non-uniform tissue radial bulging. Previous experiments showed that tensile strains of high magnitude cause an up-regulation of digestive enzyme gene expressions. Therefore, we propose that cartilage degradation near tissue lesions may be due to the large tensile strains in the principal height direction applied to cells, thus leading to an up-regulation of catabolic factors.
Department of Biomedical Engineering, Faculty of Engineering, University of Malaya, Kuala Lumpur, Malaysia; Human Performance Laboratory, Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada.
Eng Kuan
EK
Moo
Fischell Department of Bioengineering, University of Maryland, College Park, MD, United States.
Sang Kuy
SK
Han
Human Performance Laboratory, Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada; Department of Mechanical and Manufacturing Engineering, University of Calgary, Calgary, Alberta, Canada.
Salvatore
S
Federico
Human Performance Laboratory, Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada.
Scott C
SC
Sibole
Human Performance Laboratory, Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada.
Azim
A
Jinha
Department of Biomedical Engineering, Faculty of Engineering, University of Malaya, Kuala Lumpur, Malaysia.
Noor Azuan
NA
Abu Osman
Department of Biomedical Engineering, Faculty of Engineering, University of Malaya, Kuala Lumpur, Malaysia.
Belinda
B
Pingguan-Murphy
Human Performance Laboratory, Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada; Department of Mechanical and Manufacturing Engineering, University of Calgary, Calgary, Alberta, Canada. Electronic address: wherzog@ucalgary.ca.
Walter
W
Herzog
D000818:Animals; D002358:Cartilage, Articular / Q000293:injuries* / Q000502:physiology; D002417:Cattle; D019902:Chondrocytes / Q000502:physiology*; D005109:Extracellular Matrix / Q000502:physiology*; D020342:Finite Element Analysis; D008954:Models, Biological; D017711:Nonlinear Dynamics; D011312:Pressure; D013314:Stress, Mechanical; D015854:Up-Regulation / Q000502:physiology
Chondrocyte mechanics; Multi-scale finite element modelling; Osteoarthritis; Tensile strain; Tissue lesions; Transient response