Chronic softening of cartilage without thickening of underlying bone in a joint trauma model

We have recently developed a trauma model to study degradation of the rabbit patello-femoral joint. Our current working hypothesis is that alterations in retropatellar cartilage and underlying bone in our model are initiated independently by acute overstresses developed in each tissue during blunt insult to the joint, and that the processes of chronic degradation in each tissue are not related in a mechanical sense. The current study was conducted in an attempt to help validate our hypothesis by impacting the patello-femoral joint with a padded interface. Based upon earlier human cadaver experiments, we believe this would reduce the acute overstresses in patellar bone while the stresses developed in the overlying retropatellar cartilage would be sufficient enough to initiate a chronic softening of the tissue. Twenty-four animals received an impact to the patello-femoral joint and were sacrificed at either 0, 4.5, or 12 months post-insult. Three acute animals were impacted to develop a simplified computational model to estimate the stresses in joint tissues. The study showed there was a significant softening of the retropatellar cartilage at 4.5 and 12 months post-trauma, compared to unimpacted controls. However, no thickening of the underlying subchondral bone was documented at any timepoint. This was consistent with a reduction of stress in the bone compared to earlier studies, which document thickened subchondral bone post-insult at the same applied impact load. In conclusion, this study helped validate our hypothesis by documenting chronic softening of cartilage without remodeling of the underlying subchondral bone. Furthermore, this study, along with our earlier studies, suggest that impact load alone, which is currently used by the automobile industry to certify new automobiles, is not a good predictor of chronic injuries to a diarthrodial joint, and that simply the addition of padding to impact interfaces may not be adequate to protect occupants from chronic injuries.     

Rate of blunt impact loading affects changes in retropatellar cartilage and underlying bone in the rabbit patella

Our laboratory has developed a small animal model using Giant Flemish rabbits to examine chronic degradative changes in joint tissues following a blunt impact. Historically, we observe surface fissuring and decreases in the elastic modulus of retropatellar cartilage along with thickening of the underlying subchondral bone. Previous studies resulted in load insults that peaked in approximately 5ms, while loads that occur during automotive accidents or heavy exercise can produce longer rise times. The objective of the current study was to examine the influence of blunt impact loading rate using our established model. We hypothesized that the extent of fissuring and softening of retropatellar cartilage following impact would not be significantly different for a high (5ms to peak) versus low (50ms to peak) rate of loading experiment. Eight animals were impacted with a high rate of loading blunt impact, while ten animals were subjected to the same impact load at a low rate of loading. An additional eight animals served as a control population. All animals were sacrificed 12 months post-impact. The study yielded unexpected results for the first hypothesis. The high rate of loading experiments generated more surface fissuring of the retropatellar cartilage than the low rate of loading experiments. However, the degree of softening was similar for the two rates, which supported the second hypothesis. Furthermore, the study documented more thickening of bone underlying retropatellar cartilage following the high versus the low rate of loading experiments. The current study suggested that chronic injury mechanisms may be highly dependent on the rate of impact loading. These data could become extremely relevant in the development of high-velocity "safety" devices, such as knee air bags, that are needed to help position an unbelted occupant in an automobile crash.     

Chronic changes in the rabbit tibial plateau following blunt trauma to the tibiofemoral joint

The knee is often a site of injury that can often lead to a chronic disease known as osteoarthritis (OA). The disease may be initiated, in part, by acute injuries to joint cartilage and its cells. In a recent study by this laboratory, using Flemish Giant rabbits, an impact compressive load on the tibial femoral joint was shown to cause significant levels of acute damage to chondrocytes in cartilage of the medial and lateral tibial plateaus. In the current study, using the same model, histological and mechanical data from the plateaus were documented at 6 and 12 months post impact, and compared to the unimpacted control limbs and a limb from unimpacted, control animals. The mechanical properties of cartilage were measured with indentation relaxation tests on the medial and lateral plateaus in regions covered and uncovered by the meniscus. The histological studies on impacted limbs showed surface lesions on both plateaus, thickening of the underlying subchondral bone at 12 months and numerous occult microcracks at the calcified cartilage–subchondral bone interface at 6 and 12 months, without significant changes in cartilage thickness or its mechanical properties versus controls. Yet, there was an increase in both the matrix and fiber moduli and a decrease in the permeability of uncovered, medial plateau cartilage in both limbs of impacted animals between 6 and 12 months post impact that was not documented in control animals.     

Chondrocyte damage and contact pressures following impact on the rabbit tibiofemoral joint

Epidemiological studies show that tibial plateau fractures comprise about 10% of all below-knee injuries in car crashes. Studies from this laboratory document that impacts to the tibiofemoral (TF) joint at 50% of the energy producing gross fracture can generate cartilage damage and microcracks at the interface between calcified cartilage and underlying subchondral bone in the tibial plateau. These injuries are suggestive of the initiation for a long term chronic disease, such as osteoarthritis. The disease process may be further encouraged by acute damage to chondrocytes in the cartilage overlying areas of occult microcracking. The hypothesis of the current study was that significant damage to chondrocytes in tibial plateau cartilage could be generated in areas of high contact pressure by a single impact delivered to the rabbit TF joint, without a gross fracture of bone. Three rabbits received a single, 13 J of energy blunt insult to the TF joint, while another three animals were used as controls. Cell viability analyses compared chondrocyte damage in impacted versus control cartilage. Two additional rabbits were impacted to document contact pressures generated in the TF joint. The study showed high contact pressures in uncovered areas of the plateau, with a trend for higher pressures in the lateral versus medial facets. A significantly higher percentage of damaged chondrocytes existed in impacted versus the opposite, nonimpacted limbs. Additionally, more chondrocyte damage was documented in the superficial zone (top 20% of cartilage thickness) of the cartilage compared to middle (middle 50% of thickness) and deep (bottom 30% of thickness) zones. This study showed that a single blunt insult to the in situ rabbit TF joint, generating large areas of contact pressure exceeding 20 MPa, produces significant chondrocyte damage in the tibial articular cartilage, especially in the superficial zone, without gross fracture of bone. Future studies will be needed to investigate the long term, chronic outcome of this blunt force joint trauma.     

Normal contact of elastic spheres with two elastic layers as a model of joint articulation.

An analytical model of two elastic spheres with two elastic layers in normal, frictionless contact is developed which simulates contact of articulating joints, and allows for the calculation of stresses and displacements in the layered region of contact. Using various layer/layer/substrate combinations, the effects of variations in layer and substrate properties are determined in relation to the occurrence of tensile and shear stresses as the source of crack initiation in joint cartilage and bone. Vertical cracking at the cartilage surface and horizontal splitting at the tidemark have been observed in joints with primary osteoarthritis. Deep vertical cracks in the calcified cartilage and underlying bone have been observed in blunt trauma experiments. The current model shows that cartilage stresses for a particular system are a function of the ratio of contact radius to total layer thickness (a/h). Surface tension, which is observed for a/h small, is alleviated as a/h is increased due to increased load, softening and/or thinning of the cartilage layer. Decreases in a/h due to cartilage stiffening lead to increased global compressive stresses and increased incidence of surface tension, consistent with impact-induced surface cracks. Cartilage stresses are not significantly affected by variations in stiffness of the underlying material. Tensile radial strains in the cartilage layer approach one-third of the normal compressive strains, and increase significantly with cartilage softening. For cases where the middle layer stiffness exceeds that of the underlying substrate, tensile stresses occur at the base of the middle layer, consistent with impact induced cracks in the zone of calcified cartilage and subchondral bone. The presence of the superficial tangential zone appears to have little effect on underlying cartilage stresses.     

Analysis of acute mechanical insult in an animal model of post-traumatic osteoarthrosis.

Chronic degeneration of articular cartilage and bone in a rabbit model of post-traumatic osteoarthrosis has been hypothesized to occur due to acute stresses that exceed a threshold for injury. In this study, we impacted the rabbit patellofemoral joint at low and high intensities. High-intensity impacts produced degenerative changes in the joint, such as softening of retropatellar cartilage, as measured by indentation, an increase in histopathology of the cartilage, and an increase in thickness of subchondral bone underlying the cartilage. Low-intensity impacts did not cause these progressive changes. These data suggest that low-intensity impacts produced acute tissue stresses below the injury threshold, while high-intensity impacts produced stresses that exceeded the threshold for disease pathogenesis. This study begins to identify "safe" and "unsafe" ranges of acute tissue stress, using the rabbit patella, which may have future utility in the design of injury prevention devices for the human.     

The mechanical environment of chondrocytes in articular cartilage

There is a growing literature concerning chondrocyte responses to mechanical loading, but relatively little is known about the mechanical environment these cells experience in a living joint. Calculations indicate that high forces are applied to limb joints whenever the joints are flexed, because flexion can cause body weight to act on long lever arms compared to the joint centre, whereas the muscles which extend the joint act on much shorter lever arms. As a result, joint reaction forces (which compress the cartilage) can rise to 3-6 times body weight during activities such as stair climbing. Articular cartilage tends to spread this load evenly over the joint surface, but is too thin to do this well, and compressive stresses can rise to 10-20 MPa. Within cartilage, matrix stresses vary locally, possibly as a result of variation in composition or undulations in the subchondral bone, and further modifications of stress occur within each chondron. Articular cartilage is a fibrous solid and cells within it are deformed by mechanical loading rather than subjected to a hydrostatic pressure. The mechanical environment of chondrocytes can best be reproduced in vitro by direct compression of the articular surface of cartilage which is supported naturally by adjacent cartilage and subchondral bone.     

Overload arthrosis: strain patterns in the equine metacarpal condyle

An overload arthrosis occurs consistently in the palmar region of the metacarpal condyle of the equine fetlock (metacarpophalangeal) joint characterized by subchondral bone sclerosis, devitalization and mechanical failure leading to collapse of the overlying articular cartilage. Samples were selected of joints with mild, moderate, and severe subchondral sclerosis, in which cartilage collapse had not yet occurred. An additional group that had severe sclerosis with focal rarefaction suggesting impending collapse was also studied (n=5/group). Parasagittal slices were milled to 2.0 mm thickness and subjected to palmar forces 50 to 200% of those applied by the sesamoid bone at angles corresponding to early, mid and late stance support phases of the gait cycle. From contact radiographs in the loaded and unloaded samples, strains were determined by recognizing displacements in the trabecular patterns using texture correlation analysis. Failure did not occur in any of the samples. Strains were generally proportional to the forces applied and greatest at midstance. Strain patterns varied between samples and with the different loading positions. With increased subchondral bone sclerosis there was greater shear strain in overlying trabeculae. Strain patterns were not consistently different within the sclerotic bone at the site of failure. Focally higher strains at the surface were sometimes related to the edge of the platen which was molded to mimic the sesamoid bone in vivo. These results indicate that sclerotic thickening of subchondral bone transmits stresses to overlying trabeculae. No consistent strain pattern was recognized where devitalization and mechanical failure occurs. Focally higher strains related to the edge of the opposing sesamoid bone may play a role.     

Enforced exercise after blunt trauma significantly affects biomechanical and histological changes in rabbit retro-patellar cartilage

Our laboratory has developed an animal model to study factors leading to chronic disease in a blunt impacted joint. Studies to date indicate post trauma softening of the impacted joint cartilage, but a limited degree of histological degradation in the tissue. The model utilizes treadmill exercise of the animal post trauma. The hypothesis of the current study was that post trauma exercise helps limit histological and mechanical degradation of the impacted retro-patellar cartilage. The study involved a group of animals with enforced exercise on a treadmill and another group with cage-activity post trauma. The animals were sacrificed after 24 months. Mechanical and histological analyses were performed on the retro-patellar cartilage from each group. The impacted versus contra-lateral, non-impacted retro-patellar cartilage was mechanically softened in the exercise group, but not in the cage-activity group. Histological analyses of the tissue from the cage-activity group indicated that this cartilage had less surface integrity, more ossification/calcification, and more erosion than that in the impacted tissue from the exercise group. These tissue changes may lead to an apparent stiffening effect in the impacted cartilage from the cage-activity group at 24 months post-trauma. Potential relationships between the intensity and frequency of post trauma exercise and the mechanical character and histological degradation of the impacted cartilage need additional study. The study indicates that post-trauma exercise can significantly alter the outcome of a blunt knee joint trauma in this experimental animal model.     

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.     

The effect of the sagittal ridge angle on cartilage stress in the equine metacarpo-phalangeal (fetlock) joint

Fatigue failure of bones of the metacarpo-phalangeal (fetlock, MCP) joint is common in thoroughbred racehorses. Stresses within the fetlock joint cartilages are affected by the morphology of the third metacarpal bone (MC3) and proximal phalangeal bone, and the steepness of the median sagittal ridge of MC3 is believed to be associated with fracture. This study investigated the influence of the steepness of the sagittal ridge on cartilage stress distribution using a finite element model of the joint. Changes to the steepness of the sagittal ridge were made by applying a parabolic function to the mesh, creating four different models with sagittal ridge angles ranging from 95° to 105°. In the fetlock joint of Thoroughbred racehorses, sagittal ridge angles of >100° were associated with higher Von Mises stresses in cartilage at the palmar aspect of the condylar groove than such stresses in joints with sagittal ridge angles of <100°. Stresses were high in the specific region where fractures are known to originate in MC3. This aspect of morphology of the fetlock joint thus appears to play an important role in the magnitude and distribution of cartilage stresses, which, when acting on the underlying hard tissues of the articular calcified cartilage and subchondral bone may play a role in the initiation of fatigue fracture in the third metacarpal bone.     

An approach for the stress analysis of transversely isotropic biphasic cartilage under impact load.

Stress analysis of contact models for isotropic articular cartilage under impacting loads shows high shear stresses at the interface with the subchondral bone and normal compressive stresses near the surface of the cartilage. These stress distributions are not consistent, with lesions observed on the cartilage surface of rabbit patellae from blunt impact, for example, to the patello-femoral joint. The purpose of the present study was to analyze, using the elastic capabilities of a finite element code, the stress distribution in more morphologically realistic transversely isotropic biphasic contact models of cartilage. The elastic properties of an incompressible material, equivalent to those of the transversely isotropic biphasic material at time zero, were derived algebraically using stress-strain relations. Results of the stress analysis showed the highest shear stresses on the surface of the solid skeleton of the cartilage and tensile stresses in the zone of contact. These results can help explain the mechanisms responsible for surface injuries observed during blunt insult experiments.     

Do changes in the mechanical properties of articular cartilage promote catabolic destruction of cartilage and osteoarthritis?

Osteoarthritis (OA) is a joint disease characterized by cartilage degeneration, a thickening of subchondral bone, and formation of marginal osteophytes. Previous mechanical characterization of cartilage in our laboratory suggests that energy storage and dissipation is reduced in osteoarthritis as the extent of fibrillation and fissure formation increases. It is not clear whether the loss of energy storage and dissipation characteristics is a result of biochemical and/or biophysical changes that occur to hyaline cartilage in joints. The purpose of this study is to present data, on the strain rate dependence of the elastic and viscous behaviors of cartilage, in order to further characterize changes that occur in the mechanical properties that are associated with OA. We have previously hypothesized that the changes seen in the mechanical properties of cartilage may be due to altered mechanochemical transduction by chondrocytes. Results of incremental tensile stress-strain tests at strain rates between 100%/min and 10,000%/min conducted on OA cartilage indicate that the slope of the elastic stress-strain curve increases with increasing strain rate, unlike the reported behavior of skin and self-assembled collagen fibers. It is suggested that the strain-rate dependence of the elastic stress-strain curve is due to the presence of large quantities of proteoglycans (PGs), which protect articular cartilage by increasing the apparent stiffness. The increased apparent stiffness of articular cartilage at high strain rates may limit the stresses borne and prolong the onset of OA. It is further hypothesized that increased compressive loading of chondrocytes in the intermediate zone of articular cartilage occurs as a result of normal wear to the superficial zone or from excessive impact loading. Once the superficial zone of articular cartilage is worn away, the tension is decreased throughout all cartilage zones leading to increased chondrocyte compressive loading and up-regulation of mechanochemical transduction processes that elaborate catabolic enzymes.     

If good things come from above,do bad things come from below?

Factors in the synovial fluid that maintain healthy articular cartilage, such as hyaluronic acid and lubricin, come from above. Is it possible that factors which lead to the destruction of cartilage come from below in the subchondral bone? The recent acquisition of tools to probe early events in osteoarthritis is shedding new light on possible contributions from this compartment on the initiation and progression of the disease. Tanamas and co-workers now provide evidence that bone marrow lesions in the subchondral bone are predictive, both of loss of cartilage and of formation of subchondral cysts. These data provoke questions about the nature and role of bone marrow lesions.Finding the factors that initiate, or the mechanisms that lead to progression of, osteoarthritis (OA) has proven frustrating and largely unproductive. Identification of risk factors for the condition - such as prior trauma to the joint, elevated body weight and female sex - may have helped with management of OA but has done little to progress understanding of the underlying factors that drive it. OA research has been more difficult than research for some other diseases of the skeleton, for several important reasons. Early OA, at the level of symptoms, can be episodic, making it difficult to identify the disease and to follow it longitudinally. Since the main early symptom is pain, clinical trials of new therapies have been problematic. Animal experiments have been bedevilled by a lack of models that accurately replicate the human disease. And perhaps, as argued by a minority of workers in the field, disease initiators have been sought in the wrong place; that is, cartilage versus bone.The recent study of Tanamas and colleagues highlights the way in which new-generation imaging holds the promise of shedding new light on this old problem [1]. In particular, high-resolution magnetic resonance imaging (MRI) can now deliver objective, measurable information about all structures of the joint, including the amount and quality of articular cartilage, and is also a powerful tool to investigate the subchondral bone. The holy grail of clinical investigation, namely longitudinal study with quantitative endpoints, is now accessible for OA. What Tanamas and colleagues'' study shows is important because it adds to emerging evidence that processes in the subchondral bone relate strongly to changes in the volumetric amount of articular cartilage. Specifically, bone marrow lesions (BMLs), the mysterious MRI-bright regions in the subchondral bone that occur more commonly in OA, were shown to be predictive of loss of cartilage and of formation of subchondral cysts. In turn, cysts were more likely than BMLs to occur in association with loss of cartilage.These data pose the intriguing question of whether BMLs encode key clues to the aetiology of OA. Longitudinal studies have shown that the presence of BMLs constitutes a potent risk factor for structural deterioration in knee OA [2]. BML enlargement has been strongly associated with increased cartilage loss, and Tanamas and colleagues'' data further suggest that their conversion into cysts is even more predictive of cartilage loss. Significantly, a reduction in the extent of BMLs on MRI has been shown to associate with a decrease in cartilage degradation [3]. Since the origin of BMLs is not known, its investigation needs to be prioritised as an important research topic. Current informed guesses are that BMLs comprise regions of oedema, perhaps secondary to episodes of local ischaemia. Although it is not possible to biopsy BMLs in patients with early OA, several studies have sought to correlate the MRI findings with histology in more severe disease. Regions of BMLs in end-stage OA patients at knee replacement were more likely to exhibit oedema, bone necrosis and trabecular abnormalities than were control sites [4].If BMLs are secondary to local ischaemia in the subchondral bone, there are several possible consequences. Firstly, the supply of nutrients and oxygen from regions of ischaemic subchondral bone, to the overlying articular cartilage, might be reduced. Cartilage nutrition has been considered to derive from the synovial fluid. The work of Imhof and colleagues, however, suggested that more than 50% of the glucose, oxygen and water requirements of cartilage are provided by perfusion from the subchondral vessels [5]. They described the dense subchondral vasculature in close proximity to the cartilage, and the micro-channels that penetrate the subchondral mineralisation zone and permit communication between the bone and the cartilage. More recent work indicates that small molecules can diffuse, in healthy joints, bidirectionally from the synovial compartment into the cartilage and underlying bone and from the subchondral bone into the overlying cartilage [6]. Inspection of the osteochondral junction of long bones reveals that osteocytes and osteocyte canaliculi, which are also probable conduits of nutrients, are intimately associated with the articular cartilage. Experimental interruption of contact between articular cartilage and subchondral bone results in degeneration of the cartilage, and osteoblasts from OA subchondral bone conferred catabolic changes in articular chondrocytes [7].Secondly, osteocyte death in bone is becoming recognised as a signalling event for osteoclastic removal of the nonviable bone and its replacement in a remodelling episode [8]. Although subchondral bone is constantly being remodelled, concentration of this activity in a particular region of the bone could alter its mechanical integrity and its ability to properly support the overlying cartilage.Tanamas and colleagues conclude that cysts (and BMLs) may provide therapeutic targets for the treatment of knee OA [1]. Certainly, the recent acquisition of tools to probe early events in subchondral bone in OA should deliver rapid advances in our understanding of the natural history of this condition.     

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.     

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.     

Solute transport at the interface of cartilage and subchondral bone plate: Effect of micro-architecture

Cross-talk of subchondral bone and articular cartilage could be an important aspect in the etiology of osteoarthritis. Previous research has provided some evidence of transport of small molecules (~370 Da) through the calcified cartilage and subchondral bone plate in murine osteoarthritis models. The current study, for the first time, uses a neutral diffusing computed tomography (CT) contrast agent (iodixanol, ~1550 Da) to study the permeability of the osteochondral interface in equine and human samples. Sequential CT monitoring of diffusion after injecting a finite amount of contrast agent solution onto the cartilage surface using a micro-CT showed penetration of the contrast molecules across the cartilage-bone interface. Moreover, diffusion through the cartilage-bone interface was affected by thickness and porosity of the subchondral bone as well as the cartilage thickness in both human and equine samples. Our results revealed that porosity of the subchondral plate contributed more strongly to the diffusion across osteochondral interface compared to other morphological parameters in healthy equine samples. However, thickness of the subchondral plate contributed more strongly to the diffusion in slightly osteoarthritic human samples.     

Degenerative osteoarthrosis in aged ICR mice

The tibia of 117 aged ICR mice was examined histologically to provide further information on degenerative osteoarthrosis. Incidence of the lesion became higher in the male older than 480 days of age and in the female older than 450 days. Main gross changes were roughening of the articular surface, narrowing or focal thickening of the articular cartilage, and osteophytes at the margins of the joint. Histology revealed loosening of the matrix, erosion, and marginal osteophytes in the articular cartilage, and sclerotic changes of the subchondral bone.     

Adaptation of subchondral bone in osteoarthritis

Osteoarthritis is a chronic joint disease with pathological changes in the articulating cartilage and all other tissues that occupy the joint. Radin and coworkers have suggested the involvement of subchondral bone in the disease process. However, evidence for an essential role in the etiology has never been proven. Recent studies showing reduced chemical and mechanical properties of subchondral bone in various stages of the disease have invigorated interest in the role of subchondral bone in the development and progression of the disease. The current study showed that the concept of bone adaptation might explain subchondral stiffening, a process where subchondral bone becomes typically sclerotic in osteoarthritis. In addition, we report reduced mechanical matrix tissue properties as well as an increase in denatured collagen content. In conclusion, although osteoarthritic bone tissue contains increased denatured collagen and has reduced matrix mechanical properties, the widely accepted concept of subchondral stiffening is compatible with the process of normal bone adaptation.     

Impact-induced osteochondral fracture in the tibial plateau

In this study, human tibia plateaus with the meniscus removed were impacted on various regions of the plateau surface via a drop test using a 5mm indenter. Osteochondral blocks containing the failure site were then extracted, chemically fixed, dehydrated, gold-particle coated, and sent for X-ray micro-CT imaging to obtain 3-D image reconstructions of the cartilage and underlying bone. Cartilage failure upon impact appeared to be characteristically brittle in nature. Impacted cartilage from the region not protected by the meniscus showed a relatively large cavernous disruption with microcrack propagation extending radially into the subchondral bone, while impacted cartilage from beneath the meniscus showed less dramatic surface disruption and with no underlying bone failure.