Stress distribution and consolidation in cartilage constituents is influenced by cyclic loading and osteoarthritic degeneration

The understanding of load support mechanisms in cartilage has evolved with computational models that better mimic the tissue ultrastructure. Fibril-reinforced poroelastic models can reproduce cartilage behaviour in a variety of test conditions and can be used to model tissue anisotropy as well as assess stress and pressure partitioning to the tissue constituents. The goal of this study was to examine the stress distribution in the fibrillar and non-fibrillar solid phase and pressure in the fluid phase of cartilage in axisymmetric models of a healthy and osteoarthritic hip joint. Material properties, based on values from the literature, were assigned to the fibrillar and poroelastic components of cartilage and cancellous and subchondral compact bone regions. A cyclic load representing walking was applied for 25 cycles. Contact stresses in the fibrillar and non-fibrillar solid phase supported less than 1% of the contact force and increased only minimally with load cycles. Simulated proteoglycan depletion increased stresses in the radial and tangential collagen fibrils, whereas fibrillation of the tangential fibrils resulted in increased compressive stress in the non-fibrillar component and tensile stress in the radial fibrils. However neither had an effect on fluid pressure. Subchondral sclerosis was found to have the largest effect, resulting in increased fluid pressure, non-fibrillar compressive stress, tangential fibril stress and greater cartilage consolidation. Subchondral bone stiffening may play an important role in the degenerative cascade and may adversely affect tissue repair and regeneration treatments.     

Some effects of global joint morphology on local stress aberrations near imprecisely reduced intra-articular fractures

Cadaver models of contact pressure aberration near displaced intra-articular fractures complement clinical experience, but inter-specimen variability often complicates interpretation of in vitro data. A contact finite element formulation is here used to study juxta-articular stress distributions in a plane strain model of tibial plateau step-off incongruity. Attention is focused on the influence of global morphologic parameters: intact joint surface curvatures, cartilage thickness, and cartilage stiffness. The computed stress distributions agreed well with experimental recordings for a typical 3 mm incongruity in an otherwise normal joint. Both decreased cartilage thickness and increased cartilage modulus led to elevations in the peak local contact stress, and to concentration of contact stress near the edge of the step-off incongruity. Similar effects were seen when reduction of global joint congruency was modelled by decreasing the concavity of the tibial plateau. While the observed degree of coupling between global morphology and local stress aberration was by no means negligible, the sensitivity of the stresses to variations in individual parameters was relatively mild. This suggests that the finite element results will be useful for experimental data interpretation.     

Cartilage responses to a novel triaxial mechanostimulatory culture system

We have developed a novel mechanically active cartilage culture device capable of modulating the interplay between compression and shear, at physiologic stress levels (2-5 MPa). This triaxial compression culture system subjects cylindrical cartilage explants to pulsatile axial compression from platen contact, plus pulsatile radially transverse compression from external fluid compression. These compressive loads can be independently modulated to impose stress states that resemble normal physiologic loading, and to investigate perturbations of individual components of the multi-axial stress state, such as increased shear stress. Based on the observation that joint incongruity predisposes cartilage to premature degeneration, we hypothesized that cartilage extracellular matrix (ECM) synthesis would be inhibited under conditions of low transverse buttressing (high shear stress). To test this hypothesis, we compared ECM synthesis in human cartilage explants exposed to axial compression without transverse compression (high shear stress), versus explants exposed to axial compression plus an equal level of transverse compression (low shear stress). Both total (35)SO(4) incorporation and aggrecan-specific (35)SO(4) incorporation were significantly inhibited by axial compression, relative to axial plus transverse compression.     

Contact stress transients during functional loading of ankle stepoff incongruities

Cartilage deformation demonstrates viscoelastic behavior due to its unique structure. However, nearly all contact studies investigating incongruity-associated changes in cartilage surface stresses have been static tests. These tests have consistently measured only modest increases in contact stresses, even with large incongruities. In this study, an experimental approach measuring real-time contact stresses in human cadaveric ankles during quasi-physiologic motion and loading was used to determine how stepoff incongruities of the distal tibia affected contact stresses and contact stress gradients. Peak instantaneous contact stresses, in ankles with stepoffs between 1.0 and 4.0mm of the anterolateral articular surface, increased by between 2.3 x and 3.0 x compared to the corresponding intact ankle values. Peak instantaneous contact stress gradients in stepoff configurations increased by between 1.9 x and 2.6 x the corresponding intact configuration values. Anatomic reduction of the displaced fragment restored intact contact stresses and contact stress gradients. Intact and anatomic configurations demonstrated a heterogeneous population of low-magnitude, randomly oriented contact stress gradient vectors in contrast to high-magnitude, preferentially oriented gradients in stepoff configurations. Peak instantaneous contact stresses may be important pathomechanical determinants of post-traumatic arthritis. Abnormal contact stress gradients could cause regional pathological disturbances in cartilage stress and interstitial fluid distribution. Measuring contact stresses and contact stress gradients during motion allowed potential incongruity-associated pathologic changes in loading that occur over the complete motion cycle to be investigated.     

Inhomogeneous cartilage properties enhance superficial interstitial fluid support and frictional properties, but do not provide a homogeneous state of stress

It has been well established that articular cartilage is compositionally and mechanically inhomogenous through its depth. To what extent this structural inhomogeneity is a prerequisite for appropriate cartilage function and integrity is not well understood. The first hypothesis to be tested in this study was that the depth-dependent inhomogeneity of the cartilage acts to maximize the interstitial fluid load support at the articular surface, to provide efficient frictional and wear properties. The second hypothesis was that the inhomogeneity produces a more homogeneous state of elastic stress in the matrix than would be achieved with uniform properties. We have, for the first time, simultaneously determined depth-dependent tensile and compressive properties of human patellofemoral cartilage from unconfined compression stress relaxation tests. The results show that the tensile modulus increases significantly from 4.1 +/- 1.9 MPa in the deep zone to 8.3 +/- 3.7 MPa at the superficial zone, while the compressive modulus decreases from 0.73 +/- 0.26 MPa to 0.28 +/- 0.16 MPa. The experimental measurements were then implemented with the finite-element method to compute the response of an inhomogeneous and homogeneous cartilage layer to loading. The finite-element models demonstrate that structural inhomogeneity acts to increase the interstitial fluid load support at the articular surface. However, the state of stress, strain, or strain energy density in the solid matrix remained inhomogeneous through the depth of the articular layer, whether or not inhomogeneous material properties were employed. We suggest that increased fluid load support at the articular surface enhances the frictional and wear properties of articular cartilage, but that the tissue is not functionally adapted to produce homogeneous stress, strain, or strain energy density distributions. Interstitial fluid pressurization, but not a homogeneous elastic stress distribution, appears thus to be a prerequisite for the functional and morphological integrity of the cartilage.     

Physical validation of a patient-specific contact finite element model of the ankle

A validation study was conducted to determine the extent to which computational ankle contact finite element (FE) results agreed with experimentally measured tibio-talar contact stress. Two cadaver ankles were loaded in separate test sessions, during which ankle contact stresses were measured with a high-resolution (Tekscan) pressure sensor. Corresponding contact FE analyses were subsequently performed for comparison. The agreement was good between FE-computed and experimentally measured mean (3.2% discrepancy for one ankle, 19.3% for the other) and maximum (1.5% and 6.2%) contact stress, as well as for contact area (1.7% and 14.9%). There was also excellent agreement between histograms of fractional areas of cartilage experiencing specific ranges of contact stress. Finally, point-by-point comparisons between the computed and measured contact stress distributions over the articular surface showed substantial agreement, with correlation coefficients of 90% for one ankle and 86% for the other. In the past, general qualitative, but little direct quantitative agreement has been demonstrated with articular joint contact FE models. The methods used for this validation enable formal comparison of computational and experimental results, and open the way for objective statistical measures of regional correlation between FE-computed contact stress distributions from comparison articular joint surfaces (e.g., those from an intact versus those with residual intra-articular fracture incongruity).     

Injurious mechanical compression of bovine articular cartilage induces chondrocyte apoptosis

A bovine cartilage explant system was used to evaluate the effects of injurious compression on chondrocyte apoptosis and matrix biochemical and biomechanical properties within intact cartilage. Disks of newborn bovine articular cartilage were compressed in vitro to various peak stress levels and chondrocyte apoptotic cell death, tissue biomechanical properties, tissue swelling, glycosaminoglycan loss, and nitrite levels were quantified. Chondrocyte apoptosis occurred at peak stresses as low as 4.5 MPa and increased with peak stress in a dose-dependent manner. This increase in apoptosis was maximal by 24 h after the termination of the loading protocol. At high peak stresses (>20 MPa), greater than 50% of cells apoptosed. When measured in uniaxial confined compression, the equilibrium and dynamic stiffness of explants decreased with the severity of injurious load, although this trend was not significant until 24-MPa peak stress. In contrast, the equilibrium and dynamic stiffness measured in radially unconfined compression decreased significantly after injurious stresses of 12 and 7 MPa, respectively. Together, these results suggested that injurious compression caused a degradation of the collagen fibril network in the 7- to 12-MPa range. Consistent with this hypothesis, injurious compression caused a dose-dependent increase in tissue swelling, significant by 13-MPa peak stress. Glycosaminoglycans were also released from the cartilage in a dose-dependent manner, significant by 6- to 13-MPa peak stress. Nitrite levels were significantly increased above controls at 20-MPa peak stress. Together, these data suggest that injurious compression can stimulate cell death as well as a range of biomechanical and biochemical alterations to the matrix and, possibly, chondrocyte nitric oxide expression. Interestingly, chondrocyte programmed cell death appears to take place at stresses lower than those required to stimulate cartilage matrix degradation and biomechanical changes. While chondrocyte apoptosis may therefore be one of the earliest responses to tissue injury, it is currently unclear whether this initial cellular response subsequently drives cartilage matrix degradation and changes in the biomechanical properties of the tissue.     

The influence of the acetabular labrum on hip joint cartilage consolidation: a poroelastic finite element model

The goal of this study was to investigate the influence of the acetabular labrum on the consolidation, and hence the solid matrix strains and stresses, of the cartilage layers of the hip joint. A plane-strain finite element model was developed, which represented a coronal slice through the acetabular and femoral cartilage layers and the acetabular labrum. Elements with poroelastic properties were used to account for the biphasic solid/fluid nature of the cartilage and labrum. The response of the joint over an extended period of loading (10,000s) was examined to simulate the nominal compressive load that the joint is subjected to throughout the day. The model demonstrated that the labrum adds an important resistance in the flow path of the fluid being expressed from the cartilage layers of the joint. Cartilage layer consolidation was up to 40% quicker in the absence of the labrum. Following removal of the labrum from the model, the solid-on-solid contact stresses between the femoral and acetabular cartilage layers were greatly increased (up to 92% higher), which would increase the friction between the joint surfaces. In the absence of the labrum, the centre of contact shifted towards the acetabular rim. Subsurface strains and stresses were much higher without the labrum, which could contribute to fatigue damage of the cartilage layers. Finally, the labrum provided some structural resistance to lateral motion of the femoral head within the acetabulum, enhancing joint stability and preserving joint congruity.     

Cartilage interstitial fluid load support in unconfined compression

Under physiological conditions of loading, articular cartilage is subjected to both compressive strains, normal to the articular surface, and tensile strains, tangential to the articular surface. Previous studies have shown that articular cartilage exhibits a much higher modulus in tension than in compression, and theoretical analyses have suggested that this tension–compression nonlinearity enhances the magnitude of interstitial fluid pressurization during loading in unconfined compression, above a theoretical threshold of 33% of the average applied stress. The first hypothesis of this experimental study is that the peak fluid load support in unconfined compression is significantly greater than the 33% theoretical limit predicted for porous permeable tissues modeled with equal moduli in tension and compression. The second hypothesis is that the peak fluid load support is higher at the articular surface side of the tissue samples than near the deep zone, because the disparity between the tensile and compressive moduli is greater at the surface zone. Ten human cartilage samples from six patellofemoral joints, and 10 bovine cartilage specimens from three calf patellofemoral joints were tested in unconfined compression. The peak fluid load support was measured at 79±11% and 69±15% at the articular surface and deep zone of human cartilage, respectively, and at 94±4% and 71±8% at the articular surface and deep zone of bovine calf cartilage, respectively. Statistical analyses confirmed both hypotheses of this study. These experimental results suggest that the tension–compression nonlinearity of cartilage is an essential functional property of the tissue which makes interstitial fluid pressurization the dominant mechanism of load support in articular cartilage.     

A contact-coupled finite element analysis of the natural adult hip

A non-linear two-dimensional finite element model was used to study phenomena of stress redistribution in the natural adult hip resulting from parametric material property variations in the juxtarticular regions of the femoral head. Despite the geometrical simplifications employed, the intra-articular contact stresses (computed using the FEAP program) were found to be in reasonable qualitative agreement with previous in vitro data for the case of a normal hip. Generalized sclerotic changes in the subchondral plate, as reflected either in apparent modulus increases or in plate thickening, were found to have only minor effects on the computed contact stress distribution, although stress levels within the plate itself were markedly influenced. Localized subchondral plate sclerosis, by contrast, led to marked stress elevations in the cartilage immediately overlying the stiffened bone. Cartilage modulus increases caused increased load uptake for a given imposed deformation, but involved stress distribution increases which were very nearly linearly proportional to the increases in resultant load magnitude. Friction coefficient elevations had no noticeable effects on normal contact stress or upon overall load transmission, but involved complex, possibly slip-related, changes in intra-articular and cartilaginous shear stresses.     

A mechanical apparatus with microprocessor controlled stress profile for cyclic compression of cultured articular cartilage explants

An apparatus was designed for mechanical compression of cultured articular cartilage explants with acylindrical plain-ended loading head (diameter 2-5 mm) driven by a stepping motor. A load cell under the culture dish was applied for feedback regulation utilizing a microprocessor-based control unit. The operating programs allowed either continuous or cyclic loading, the latter with adjustable loading/resting ratio. The improvements in the present design compared with previously described apparatuses for similar purposes include: (1) the accurately controlled compression by a load cell and a rapid feedback circuit; (2) the wide range of selectable stresses (25 kPa-12.5 MPa) with both continuous and cyclic loading modes; (3) the ability to handle cycles as short as 1 s with 15 ms peak loading phase. Using a 4 s cycle and 0.5 MPa load for 1.5 h resulted in a significantly enhanced incorporation of radiosulphate in cultured bovine articular cartilage explants, suggesting a stimulation of proteoglycan synthesis. Light and scanning electron microscopic examinations revealed a slight depression and superficial alterations in cartilage structure at the impact site following high pressures. We expect that this apparatus will help in revealing how articular cartilage tissue and chondrocytes respond to external mechanical stimuli.     

An in vitro investigation of the acetabular labral seal in hip joint mechanics

Labrum pathology may contribute to early joint degeneration through the alteration of load transfer between, and the stresses within, the cartilage layers of the hip. We hypothesize that the labrum seals the hip joint, creating a hydrostatic fluid pressure in the intra-articular space, and limiting the rate of cartilage layer consolidation. The overall cartilage creep consolidation of six human hip joints was measured during the application of a constant load of 0.75 times bodyweight, or a cyclic sinusoidal load of 0.75+/-0.25 times bodyweight, before and after total labrum resection. The fluid pressure within the acetabular was measured. Following labrum resection, the initial consolidation rate was 22% greater (p=0.02) and the final consolidation displacement was 21% greater (p=0.02). There was no significant difference in the final consolidation rate. Loading type (constant vs. cyclic) had no significant effect on the measured consolidation behaviour. Fluid pressurisation was observed in three of the six hips. The average pressures measured were: for constant loading, 541+/-61kPa in the intact joint and 216+/-165kPa following labrum resection, for cyclic loading, 550+/-56kPa in the intact joint and 195+/-145kPa following labrum resection. The trends observed in this experiment support the predictions of previous finite element analyses. Hydrostatic fluid pressurisation within the intra-articular space is greater with the labrum than without, which may enhance joint lubrication. Cartilage consolidation is quicker without the labrum than with, as the labrum adds an extra resistance to the flow path for interstitial fluid expression. However, both sealing mechanisms are dependent on the fit of the labrum against the femoral head.     

Fatigue of bovine trabecular bone

Fatigue loading of bone, from the activities of daily living in the elderly, or from prolonged exercise in the young, can lead to increased risk of fracture. Elderly patients with osteoporosis are particularly prone to fragility fractures of the vertebrae, where load is carried primarily by trabecular bone. In this study, specimens of bovine trabecular bone were loaded in compressive fatigue at four different normalized stresses to one of six maximum strains. The resulting change in modulus and residual strain accumulation were measured over the life of the fatigue test. The number of cycles to reach a given maximum compressive strain increased with decreasing normalized stress. Modulus reduction and specimen residual strain increased with increasing maximum compressive strain, but few differences were observed between specimens loaded to the same maximum strain at different normalized stresses.     

Micromechanical response of mineral and collagen phases in bone

We report the first simultaneous quantification of Young's modulus in the separate material phases of bone: collagen and carbonated hydroxyapatite. High-energy X-ray scattering and in situ loading revealed macroscopic, mineral, and collagen Young's moduli (90% confidence limit) for a canine fibula equaled 24.7(0.2) GPa, 38.2(0.5) GPa {for 00.4 and 43.6(1.4) GPa for 22.2}, and 18(1.2) GPa, respectively. The mineral contained compressive residual stresses on the order of -60 to -80 MPa before loading and had a stress enhancement (ratio of internal to applied stress) between 2.0 and 2.3. The diffraction peak width increased with increasing applied stress, mainly along the bone's longitudinal direction, and peak widths returned to pre-deformation values when load was removed. In a second fibula section from the same animal, the mineral's internal stress changed from -50 MPa (22.2 reflection) to -75 MPa (00.4) just after removal from formalin to -10 MPa after eight hours immersion in phosphate-buffered saline; the corresponding change in collagen D-spacing DeltaD/D equaled 4.2x10(-3).     

Evaluation of a subject-specific finite-element model of the equine metacarpophalangeal joint under physiological load

The equine metacarpophalangeal (MCP) joint is frequently injured, especially by racehorses in training. Most injuries result from repetitive loading of the subchondral bone and articular cartilage rather than from acute events. The likelihood of injury is multi-factorial but the magnitude of mechanical loading and the number of loading cycles are believed to play an important role. Therefore, an important step in understanding injury is to determine the distribution of load across the articular surface during normal locomotion. A subject-specific finite-element model of the MCP joint was developed (including deformable cartilage, elastic ligaments, muscle forces and rigid representations of bone), evaluated against measurements obtained from cadaver experiments, and then loaded using data from gait experiments. The sensitivity of the model to force inputs, cartilage stiffness, and cartilage geometry was studied. The FE model predicted MCP joint torque and sesamoid bone flexion angles within 5% of experimental measurements. Muscle–tendon forces, joint loads and cartilage stresses all increased as locomotion speed increased from walking to trotting and finally cantering. Perturbations to muscle–tendon forces resulted in small changes in articular cartilage stresses, whereas variations in joint torque, cartilage geometry and stiffness produced much larger effects. Non-subject-specific cartilage geometry changed the magnitude and distribution of pressure and the von Mises stress markedly. The mean and peak cartilage stresses generally increased with an increase in cartilage stiffness. Areas of peak stress correlated qualitatively with sites of common injury, suggesting that further modelling work may elucidate the types of loading that precede joint injury and may assist in the development of techniques for injury mitigation.     

Determination of real-time in-vivo cartilage contact deformation in the ankle joint

The knowledge of real-time in-vivo cartilage deformation is important for understanding of cartilage function and biomechanical factors that may relate to cartilage degeneration. This study investigated cartilage contact area and peak contact compressive strain of four healthy human ankle joints as a function of time using a combined magnetic resonance (MR) and dual-orthogonal fluoroscopic imaging technique. Each ankle was subjected to a different constant loading (between 700 and 820 N). The cartilage contact deformation was obtained from the first second to 300 s after the load was applied. In all ankle joints studied in this paper, contact strains increased to 24-38% at first 20 s after loading. Beyond 20 s, the change of cartilage contact deformation was relatively small and varied in a rate close to zero beyond 50 s. These data indicated that the cartilage contact areas and contact strain could raise dramatically right after loading and reach a relatively stable condition within 1 min after constant loading. The history of cartilage deformation determined in this study may provide a real-time boundary condition for 3D finite element simulation of in vivo cartilage contact stress in the joint as a function of time.     

The influence of cartilage surface topography on fluid flow in the intra-articular gap

Self-lubrication of a diarthrodial joint is largely attributed to interstitial fluid pressurisation. However, the retention of synovial fluid within the intra-articular gap may also contribute to lubrication. Fluid flow in the intra-articular gap between two micro-rough cartilage surfaces was simulated with a three-dimensional numerical model. Representative surface roughness parameters were incorporated and their relative influence on gap flow resistance was quantified. Resistance changes with decreasing gap height were explored. Cartilage surface micro-topography improves the retention of viscous synovial fluid in the gap, through increased resistance to tangential flow. Local asperity contact greatly increases resistance through tortuosity of the flow path.     

Effect of impact load on articular cartilage: cell metabolism and viability, and matrix water content.

Significant evidence exists that trauma to a joint produced by a single impact load below that which causes subchondral bone fracture can result in permanent damage to the cartilage matrix, including surface fissures, loss of proteoglycan, and cell death. Limited information exists, however, on the effect of a varying impact stress on chondrocyte biophysiology and matrix integrity. Based on our previous work, we hypothesized that a stress-dependent response exists for both the chondrocyte's metabolic activity and viability and the matrix's hydration. This hypothesis was tested by impacting bovine cartilage explants with nominal stresses ranging from 0.5 to 65 MPa and measuring proteoglycan biosynthesis, cell viability, and water content immediately after impaction and 24 hours later. We found that proteoglycan biosynthesis decreased and water content increased with increasing impact stress. However, there appeared to be a critical threshold stress (15-20 MPa) that caused cell death and apparent rupture of the collagen fiber matrix at the time of impaction. We concluded that the cell death and collagen rupture are responsible for the observed alterations in the tissue's metabolism and water content, respectively, although the exact mechanism causing this damage could not be determined.     

Competing regulation of matrix biosynthesis by mechanical and IGF-1 signalling in elderly human articular cartilage in vitro

This study investigates the separate and combined effects of IGF-1 and mechanical loads on chondrocytes in elderly human femoral head articular cartilage. Full depth biopsies of articular cartilage were subjected to either no load, static or cyclic (2 s on/2 s off) loading in unconfined compression at a stress of 1 MPa for 48 h with or without IGF-1 (300 ng ml(-1)). Chondrocyte biosynthetic activity was measured using 35S-sulphate and 3H-leucine during the last 24 h of loading. IGF-1 alone increased the rates of isotope incorporation, by 80% for 35S-SO4 and 40% for 3H-leucine, whereas loading alone reduced matrix biosynthesis. Applying load (cyclic or static) in the presence of IGF-1 returned the incorporation rates to their unstimulated levels. This study suggests elderly human articular cartilage is responsive to stimulation by IGF-1 but mechanical factors seem to act sufficiently strongly in the opposite direction to cancel this response.     

Effects of shear stress on articular chondrocyte metabolism

The articular cartilage of diarthrodial joints experiences a variety of stresses, strains and pressures that result from normal activities of daily living. In normal cartilage, the extracellular matrix exists as a highly organized composite of specialized macromolecules that distributes loads at the bony ends. The chondrocyte response to mechanical loading is recognized as an integral component in the maintenance of articular cartilage matrix homeostasis. With inappropriate mechanical loading of the joint, as occurs with traumatic injury, ligament instability, bony malalignment or excessive weight bearing, the cartilage exhibits manifestations characteristic of osteoarthritis. Breakdown of cartilage in osteoarthritis involves degradation of the extracellular matrix macromolecules and decreased expression of chondrocyte proteins necessary for normal joint function. Osteoarthritic cartilage often exhibits increased amounts of type I collagen and synthesis of proteoglycans characteristic of immature cartilage. The shift in cartilage phenotype in response to altered load yields a matrix that fails to support normal joint function. Mathematical modeling and experimental studies in animal models confirm an association between altered loading of diarthrotic joints and arthritic changes. Both types of studies implicate shear forces as a critical component in the destructive profile. The severity of cartilage destruction in response to altered loads appears linked to expression of biological factors influencing matrix integrity and cellular metabolism. Determining how shear stress alters chondrocyte metabolism is fundamental to understanding how to limit matrix destruction and stimulate cartilage repair and regeneration. At present, the precise biochemical and molecular mechanisms by which shear forces alter chondrocyte metabolism from a normal to a degenerative phenotype remain unclear. The results presented here address the hypothesis that articular chondrocyte metabolism is modulated by direct effects of shear forces that act on the cell through mechanotransduction processes. The purpose of this work is to develop critical knowledge regarding the basic mechanisms by which mechanical loading modulates cartilage metabolism in health and disease. This presentation will describe the effects of using fluid induced shear stress as a model system for stimulation of articular chondrocytes in vitro. The fluid induced shear stress was applied using a cone viscometer system to stimulate all the cells uniformly under conditions of minimal turbulence. The experiments were carried using high-density primary monolayer cultures of normal and osteoarthritic human and normal bovine articular chondrocytes. The analysis of the cellular response included quantification of cytokine release, matrix metalloproteinase expression and activation of intracellular signaling pathways. The data presented here show that articular chondrocytes exhibit a dose- and time-dependent response to shear stress that results in the release of soluble mediators and extracellular matrix macromolecules. The data suggest that the chondrocyte response to mechanical stimulation contributes to the maintenance of articular cartilage homeostasis in vivo.