Viscoelastic properties of chondrocytes from normal and osteoarthritic human cartilage

Abstract

The deformation behavior and mechanical properties of articular chondrocytes are believed to play an important role in their response to mechanical loading of the extracellular matrix. This study utilized the micropipette aspiration test to measure the viscoelastic properties of chondrocytes isolated from macroscopically normal or end-stage osteoarthritic cartilage. A three-parameter standard linear solid was used to model the viscoelastic behavior of the cells. Significant differences were found between the mechanical properties of chondrocytes isolated from normal and osteoarthritic cartilage. Specifically, osteoarthritic chondrocytes exhibited a significantly higher equilibrium modulus (0.33 +/- 0.23 compared with 0.24 +/- 0.11 kPa), instantaneous modulus (0.63 +/- 0.51 compared with 0.41 +/- 0.17 kPa), and apparent viscosity (5.8 +/- 6.5 compared with 3.0 +/- 1.8 kPa-s) compared with chondrocytes isolated from macroscopically normal, nonosteoarthritic cartilage. The elastic moduli and relaxation time constant determined experimentally in this study were used to estimate the apparent biphasic properties of the chondrocyte on the basis of the equation for the gel relaxation time of a biphasic material. The differences in viscoelastic properties may reflect alterations in the structure and composition of the chondrocyte cytoskeleton that have previously been associated with osteoarthritic cartilage. Coupled with earlier theoretical models of cell-matrix interactions in articular cartilage, the increased elastic and viscous properties suggest that the mechanical environment of the chondrocyte may be altered in osteoarthritic cartilage.

The role of the cytoskeleton in the viscoelastic properties of human articular chondrocytes

“…The increased stiffness (moduli) of osteoarthritic chondrocytes relative to non-osteoarthritic chondrocytes is generally consistent with those reported previously [48]. Although little difference in cytoskeletal distribution was seen in this study between non-osteoarthritic and osteoarthritic cells, previous studies with electron and confocal microscopy showed cytoskeletal alterations that were associated with cartilage degeneration.…”

“…It is important to note that osteoarthritic cartilage is generally lacking a surface, or superficial zone, suggesting that the population of cells studied in this case includes a greater proportion of middle or deep zone cells as compared to non-osteoarthritic cartilage. In recent studies, we have shown little or no zonal variations in the mechanical properties of porcine chondrocytes from surface zone cartilage as compared to middle/deep zone tissue (Guilak, unpublished results), suggest that the observed differences between osteoarthritic and non-osteoarthritic chondrocytes are not simply due to alterations in the ratio of surface versus middle/deep cells studied [48].…”

“…Prior to testing the chondrocytes, alginate beads were incubated for 3 h in control, low, medium and high concentrations of chemical agents that disrupt the three principal cytoskeletal elements (cytochalasin D for microfilaments [44] Micropipette aspiration was used to determine the viscoelastic properties of the chondrocytes, as described previously [48]. Briefly, the solution and cells were placed in a chamber that allows for the entry of a micropipette from the side [20].…”

“…DPI 5-28, Validyne Engineering Corp.. Northridge, CAI. as described previously [48]. During the application of pressure, video images of cell aspiration into the micropipette were recorded on a S-VHS video cassette recorder at 60 fields/s with a CCD camera (COHU.…”

“…I Journril q f Orllwpuedic R~WLWCII 22 (2004) [131][132][133][134][135][136][137][138][139] matrices [12]. In previous studies, we have shown that the mechanical behavior of the chondrocyte is that of a viscoelastic solid [26,48], and it has been assumed that the chondrocyte cytoskeleton is responsible for this "solid-like'' elastic response due to its distribution and structure within the cell [lo]. However, the sources of viscoelasticity in the cell are not fully understood and may be attributed to flow-dependent (fluid-solid interactions and fluid viscosity) [28,46] as well as flow-independent mechanisms (viscoelasticity of the cytoskeleton) [5,8,20,43,45,47].…”