The effect of meniscal tears and resultant partial meniscectomies on the knee contact stresses: a finite element analysis

Knee osteoarthritis (OA) is believed to result from high levels of contact stresses on the articular cartilage and meniscus after meniscal damage. This study investigated the effect of meniscal tears and partial meniscectomies on the peak compressive and shear stresses in the human knee joint. An elaborate three-dimensional finite element model of knee joint including bones, articular cartilages, menisci and main ligaments was developed from computed tomography and magnetic resonance imaging images. This model was used to model four types of meniscal tears and their resultant partial meniscectomies and analysed under an axial 1150 N load at 0° flexion. Three different conditions were compared: a healthy knee joint, a knee joint with medial meniscal tears and a knee joint following partial meniscectomies. The numerical results showed that each meniscal tear and its resultant partial meniscectomy led to an increase in the peak compressive and shear stresses on the articular cartilages and meniscus in the medial knee compartment, especially for partial meniscectomy. Among the four types of meniscal tears, the oblique tear resulted in the highest values of the peak compressive and shear stresses. For the four partial meniscectomies, longitudinal meniscectomy led to the largest increase in these two stresses. The lateral compartment was minimally affected by all the simulations. The results of this study demonstrate meniscal tear and its resultant partial meniscectomy has a positive impact on the maintenance of high levels of contact stresses, which may improve the progression of knee OA, especially for partial meniscectomy. Surgeons should adopt a prudent strategy to preserve the greatest amount of meniscus possible.     

Tibiofemoral joint contact force in deep knee flexion and its consideration in knee osteoarthritis and joint replacement

The aim of the study was to estimate the tibiofemoral joint force in deep flexion to consider how the mechanical load affects the knee. We hypothesize that the joint force should not become sufficiently large to damage the joint under normal contact area, but should become deleterious to the joint under the limited contact area. Sixteen healthy knees were analyzed using a motion capture system, a force plate, a surface electromyography, and a knee model, and then tibiofemoral joint contact forces were calculated. Also, a contact stress simulation using the contact areas from the literature was performed. The peak joint contact forces (M +/- SD) were 4566 +/- 1932 N at 140 degrees in rising from full squat and 4479 +/- 1478 N at 90 degrees in rising from kneeling. Under normal contact area, the tibiofemoral contact stresses in deep flexion were less than 5 MPa and did not exceed the stress to damage the cartilage. The contact stress simulation suggests that knee prosthesis having the contact area smaller than 200 mm2 may be problematic since the contact stress in deep flexion would become larger than 21 MPa, and it would lead damage or wear of the polyethylene.     

Degeneration of normal articular cartilage induced by late phase osteoarthritic synovial fluid in beagle dogs

Objective

To investigate the pathogenesis of late phase osteoarthritic (OA) synovial fluid (SF) on normal articular cartilage in vivo and provide an understanding of degenerative cartilage extending in OA joint.

Methods

A random knee, each of 8 beagle dogs, received anterior cruciate ligament transection (ACLT) and was confirmed to have late phase OA degenerative changes at 24 weeks after operation. Thereafter, one random elbow of each canine was injected with autologous late phase OA knee SF. The contralateral elbow was injected with normal saline (NS) of the same volume as SF aspirated from ACLT knee. These two groups of elbows were labeled “SF” and “NS”. 8 other beagle dogs were left intact and placed in Group Control. After aseptic arthrocentesis was performed weekly on both elbows for 24 weeks, morphological changes were observed in the cartilage of the elbows, and expressions of 7 biological etiological factors of chondrocytes of the elbows were determined in Group SF, Group NS and Group Control, respectively.

Results

Morphological changes were observed in articular cartilage of the elbows in Group SF. Levels of unit area of collagen type I in the noncalcified, calcified and full zones of articular cartilage of the elbows in Group SF increased significantly. Level of unit area of collagen type III in the calcified zone of articular cartilage of the elbows in Group SF remained unchanged. Meanwhile, expressions of MMP-1 and MMP-3 of chondrocytes of the elbows in Group SF increased significantly. There was almost no difference between articular cartilage in Group NS and Group Control.

Conclusion

Based on these results, we conclude that OA degeneration of normal articular cartilage can be independently induced by late phase OA SF. Endogenous OA biological etiological factor may be one of the reasons causing degenerative cartilage extending in OA joint.     

Material and functional properties of articular cartilage and patellofemoral contact mechanics in an experimental model of osteoarthritis

The purposes of this study were to determine the in situ functional and material properties of articular cartilage in an experimental model of joint injury, and to quantify the corresponding in situ joint contact mechanics. Experiments were performed in the anterior cruciate ligament (ACL) transected knee of the cat and the corresponding, intact contralateral knee, 16 weeks following intervention. Cartilage thickness, stiffness, effective Young’s modulus, and permeability were measured and derived from six locations of the knee. The total contact area and peak pressures in the patellofemoral joint were obtained in situ using Fuji Pressensor film, and comparisons between experimental and contralateral joint were made for corresponding loading conditions. Total joint contact area and peak pressure were increased and decreased significantly (=0.01), respectively, in the experimental compared to the contralateral joint. Articular cartilage thickness and stiffness were increased and decreased significantly (=0.01), respectively, in the experimental compared to the contralateral joint in the four femoral and patellar test locations. Articular cartilage material properties (effective Young’s modulus and permeability) were the same in the ACL-transected and intact joints. These results demonstrate for the first time the effect of changes in articular cartilage properties on the load transmission across a joint. They further demonstrate a substantial change in the joint contact mechanics within 16 weeks of ACL transection. The results were corroborated by theoretical analysis of the contact mechanics in the intact and ACL-transected knee using biphasic contact analysis and direct input of cartilage properties and joint surface geometry from the experimental animals. We conclude that the joint contact mechanics in the ACL-transected cat change within 16 weeks of experimental intervention.     

Lubricin: a novel potential biotherapeutic approaches for the treatment of osteoarthritis

Osteoarthritis (OA) is a multi-factor disorder of sinovial joints, which characterized by escalated degeneration and loss of articular cartilage. Treatment of OA is a critical unmet need in medicine for regeneration of damaged articular cartilage in elderly. On the other hand, lubricin, a glycoprotein specifically synthesized by chondrocytes located at the surface of articular cartilage, has been shown to provide boundary lubrication of congruent articular surfaces under conditions of high contact pressure and near zero sliding speed. Lubrication of these surfaces is critical to normal joint function, while different gene expressions of lubricin had been found in the synovium of rheumatoid arthritis (RA) and OA. Moreover, mutations or lacking of lubricin gene have been shown to link to the joint disease such as camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP), synovial hyperplasia and failure of joint function, suggesting an important role of lubricin in the pathogenesis of these joint disease. Recent studies demonstrate that administration with recombinant lubricin in the joint cavity would be effective in the prevention of cartilage degeneration in animal OA models. Therefore, a treatment with lubricin which would protect cartilage in vivo would be desirable. This article reviews recent findings with regard to the possible role of lubricin in the progression of OA, and further discusses lubricin as a novel potential biotherapeutic approaches for the treatment of OA.     

Application of a semi-automatic cartilage segmentation method for biomechanical modeling of the knee joint

Manual segmentation of articular cartilage from knee joint 3D magnetic resonance images (MRI) is a time consuming and laborious task. Thus, automatic methods are needed for faster and reproducible segmentations. In the present study, we developed a semi-automatic segmentation method based on radial intensity profiles to generate 3D geometries of knee joint cartilage which were then used in computational biomechanical models of the knee joint. Six healthy volunteers were imaged with a 3T MRI device and their knee cartilages were segmented both manually and semi-automatically. The values of cartilage thicknesses and volumes produced by these two methods were compared. Furthermore, the influences of possible geometrical differences on cartilage stresses and strains in the knee were evaluated with finite element modeling. The semi-automatic segmentation and 3D geometry construction of one knee joint (menisci, femoral and tibial cartilages) was approximately two times faster than with manual segmentation. Differences in cartilage thicknesses, volumes, contact pressures, stresses, and strains between segmentation methods in femoral and tibial cartilage were mostly insignificant (p > 0.05) and random, i.e. there were no systematic differences between the methods. In conclusion, the devised semi-automatic segmentation method is a quick and accurate way to determine cartilage geometries; it may become a valuable tool for biomechanical modeling applications with large patient groups.     

A detailed and validated three dimensional dynamic model of the patellofemoral joint

A detailed 3D anatomical model of the patellofemoral joint was developed to study the tracking, force, contact and stability characteristics of the joint. The quadriceps was considered to include six components represented by 15 force vectors. The patellar tendon was modeled using four bundles of viscoelastic tensile elements. Each of the lateral and medial retinaculum was modeled by a three-bundle nonlinear spring. The femur and patella were considered as rigid bodies with their articular cartilage layers represented by an isotropic viscoelastic material. The geometrical and tracking data needed for model simulation, as well as validation of its results, were obtained from an in vivo experiment, involving MR imaging of a normal knee while performing isometric leg press against a constant 140 N force. The model was formulated within the framework of a rigid body spring model and solved using forth-order Runge-Kutta, for knee flexion angles between zero and 50 degrees. Results indicated a good agreement between the model predictions for patellar tracking and the experimental results with RMS deviations of about 2 mm for translations (less than 0.7 mm for patellar mediolateral shift), and 4 degrees for rotations (less than 3 degrees for patellar tilt). The contact pattern predicted by the model was also consistent with the results of the experiment and the literature. The joint contact force increased linearly with progressive knee flexion from 80 N to 210 N. The medial retinaculum experienced a peak force of 18 N at full extension that decreased with knee flexion and disappeared entirely at 20 degrees flexion. Analysis of the patellar time response to the quadriceps contraction suggested that the muscle activation most affected the patellar shift and tilt. These results are consistent with the recent observations in the literature concerning the significance of retinaculum and quadriceps in the patellar stability.     

A finite element model of the human knee joint for the study of tibio-femoral contact

As a step towards developing a finite element model of the knee that can be used to study how the variables associated with a meniscal replacement affect tibio-femoral contact, the goals of this study were 1) to develop a geometrically accurate three-dimensional solid model of the knee joint with special attention given to the menisci and articular cartilage, 2) to determine to what extent bony deformations affect contact behavior, and 3) to determine whether constraining rotations other than flexion/extension affects the contact behavior of the joint during compressive loading. The model included both the cortical and trabecular bone of the femur and tibia, articular cartilage of the femoral condyles and tibial plateau, both the medial and lateral menisci with their horn attachments, the transverse ligament, the anterior cruciate ligament, and the medial collateral ligament. The solid models for the menisci and articular cartilage were created from surface scans provided by a noncontacting, laser-based, three-dimensional coordinate digitizing system with an root mean squared error (RMSE) of less than 8 microns. Solid models of both the tibia and femur were created from CT images, except for the most proximal surface of the tibia and most distal surface of the femur which were created with the three-dimensional coordinate digitizing system. The constitutive relation of the menisci treated the tissue as transversely isotropic and linearly elastic. Under the application of an 800 N compressive load at 0 degrees of flexion, six contact variables in each compartment (ie., medial and lateral) were computed including maximum pressure, mean pressure, contact area, total contact force, and coordinates of the center of pressure. Convergence of the finite element solution was studied using three mesh sizes ranging from an average element size of 5 mm by 5 mm to 1 mm by 1 mm. The solution was considered converged for an average element size of 2 mm by 2 mm. Using this mesh size, finite element solutions for rigid versus deformable bones indicated that none of the contact variables changed by more than 2% when the femur and tibia were treated as rigid. However, differences in contact variables as large as 19% occurred when rotations other than flexion/extension were constrained. The largest difference was in the maximum pressure. Among the principal conclusions of the study are that accurate finite element solutions of tibio-femoral contact behavior can be obtained by treating the bones as rigid. However, unrealistic constraints on rotations other than flexion/extension can result in relatively large errors in contact variables.     

Analysis of muscle activation patterns during transitions into and out of high knee flexion postures

Increased risk of medial tibiofemoral osteoarthritis (OA) is linked to occupations that require frequent transitions into and out of postures which require high knee flexion (>90°). Muscle forces are major contributors to joint loading, and an association between compressive forces due to muscle activations and the degeneration of joint cartilage has been suggested. The purpose of this study was to evaluate muscle activation patterns of muscles crossing the knee during transitions into and out of full-flexion kneeling and squatting, sitting in a low chair, and gait. Both net and co-activation were greater when transitioning out of high flexion postures, with maximum activation occurring at knee angles greater than 100°. Compared to gait, co-activation levels during high flexion transitions were up to approximately 3 times greater. Co-activation was significantly greater in the lateral muscle group compared to the medial group during transitions into and out of high flexion postures. These results suggest that compression due to activation of the medial musculature of the knee may not be the link between high knee flexion postures and increased medial knee OA observed in occupational settings. Further research on a larger subject group and workers with varying degrees of knee OA is necessary.     

Deletion of Dual Specificity Phosphatase 1 Does Not Predispose Mice to Increased Spontaneous Osteoarthritis

Background

Osteoarthritis (OA) is a degenerative joint disease with poorly understood etiology and pathobiology. Mitogen activated protein kinases (MAPKs) including ERK and p38 play important roles in the mediation of downstream pathways involved in cartilage degenerative processes. Dual specificity phosphatase 1 (DUSP1) dephosphorylates the threonine/serine and tyrosine sites on ERK and p38, causing deactivation of downstream signalling. In this study we examined the role of DUSP1 in spontaneous OA development at 21 months of age using a genetically modified mouse model deficient in Dusp1 (DUSP1 knockout mouse).

Results

Utilizing histochemical stains of paraffin embedded knee joint sections in DUSP1 knockout and wild type female and male mice, we showed similar structural progression of cartilage degeneration associated with OA at 21 months of age. A semi-quantitative cartilage degeneration scoring system also demonstrated similar scores in the various aspects of the knee joint articular cartilage in DUSP1 knockout and control mice. Examination of overall articular cartilage thickness in the knee joint demonstrated similar results between DUSP1 knockout and wild type mice. Immunostaining for cartilage neoepitopes DIPEN, TEGE and C1,2C was similar in the cartilage lesion sites and chondrocyte pericellular matrix of both experimental groups. Likewise, immunostaining for phosphoERK and MMP13 showed similar intensity and localization between groups. SOX9 immunostaining demonstrated a decreased number of positive cells in DUSP1 knockout mice, with correspondingly decreased staining intensity. Analysis of animal walking patterns (gait) did not show a discernable difference between groups.

Conclusion

Loss of DUSP1 does not cause changes in cartilage degeneration and gait in a mouse model of spontaneous OA at 21 months of age. Altered staining was observed in SOX9 immunostaining which may prove promising for future studies examining the role of DUSPs in cartilage and OA, as well as models of post-traumatic OA.     

MicroRNA-146a is linked to pain-related pathophysiology of osteoarthritis

Because miR-146a is linked to osteoarthritis (OA) and cartilage degeneration is associated with pain, we have characterized the functional role of miR-146a in the regulation of human articular cartilage homeostasis and pain-related factors. Expression of miRNA 146a was analyzed in human articular cartilage and synovium, as well as in dorsal root ganglia (DRG) and spinal cord from a rat model for OA-related pain assessment. The functional effects of miR-146a on human chondrocytic, synovial, and microglia cells were studied in cells transfected with miR-146a. Using real-time PCR, we assessed the expression of chondrocyte metabolism-related genes in chondrocytes, genes for inflammatory factors in synovial cells, as well as pain-related proteins and ion channels in microglial cells. Previous studies showed that miR-146a is significantly upregulated in human peripheral knee OA joint tissues. Transfection of synthetic miR-146a significantly suppresses extracellular matrix-associated proteins (e.g., Aggrecan, MMP-13, ADAMTS-5, collagen II) in human knee joint chondrocytes and regulates inflammatory cytokines in synovial cells from human knee joints. In contrast, miR-146a is expressed at reduced levels in DRGs and dorsal horn of the spinal cords isolated from rats experiencing OA-induced pain. Exogenous supplementation of synthetic miR-146a significantly modulates inflammatory cytokines and pain-related molecules (e.g., TNFα, COX-2, iNOS, IL-6, IL8, RANTS and ion channel, TRPV1) in human glial cells. Our findings suggest that miR-146a controls knee joint homeostasis and OA-associated algesia by balancing inflammatory responses in cartilage and synovium with pain-related factors in glial cells. Hence, miR-146a may be useful for the treatment of both cartilage regeneration and pain symptoms caused by OA.     

Three-dimensional mathematical model analysis of the patellofemoral joint

This paper is concerned with a mathematical model analysis of the patellofemoral joint in the human knee, taking into account the articular surface geometry and mechanical properties of the ligament. It was made by the application of a computer-aided design theory (previously studied) and it was possible to express the articular surface geometries in a mathematical formulation and hence elucidate the joint movement mechanics. This method was then applied to a three-dimensional geometrical model of the patellofemoral joint. For the modelling of tendofemoral contact at large angles of knee flexion, the geodestic line theory was adopted. Applying the Newton-Raphson method and the Runge-Kutta Gil method to the model, variables such as patellar attitudes, patellofemoral contact force and tensile force of the patellar ligament for various knee flexion angles were computed. Applying the Hertzian elastic theory, contact stress was also computed. These results showed good agreement with the previously reported experimental results. As an application for the model, some parameter analyses were performed in terms of the contact stress variations and compared with those of the normal knee. The simulation results indicated that both the Q-angle increase and decrease increased contact stress, the patella alta showed undulating variations of stress while the patella infera showed little change of stress, and the tibial tuberositas elevation showed 20-30% reduction of stress.     

Statistical shape modeling describes variation in tibia and femur surface geometry between Control and Incidence groups from the Osteoarthritis Initiative database

We hypothesize that variability in knee subchondral bone surface geometry will differentiate between patients at risk and those not at risk for developing osteoarthritis (OA) and suggest that statistical shape modeling (SSM) methods form the basis for developing a diagnostic tool for predicting the onset of OA. Using a subset of clinical knee MRI data from the osteoarthritis initiative (OAI), the objectives of this study were to (1) utilize SSM to compactly and efficiently describe variability in knee subchondral bone surface geometry and (2) determine the efficacy of SSM and rigid body transformations to distinguish between patients who are not expected to develop osteoarthritis (i.e. Control group) and those with clinical risk factors for OA (i.e. Incidence group). Quantitative differences in femur and tibia surface geometry were demonstrated between groups, although differences in knee joint alignment measures were not statistically significant, suggesting that variability in individual bone geometry may play a greater role in determining joint space geometry and mechanics. SSM provides a means of explicitly describing complete articular surface geometry and allows the complex spatial variation in joint surface geometry and joint congruence between healthy subjects and those with clinical risk of developing or existing signs of OA to be statistically demonstrated.     

The role of lubricant entrapment at biological interfaces: reduction of friction and adhesion in articular cartilage

Friction and adhesion of articular cartilage from high- and low-load-bearing regions of bovine knee joints were examined with a tribometer under various loads and equilibration times. The effect of trapped lubricants was investigated by briefly unloading the cartilage sample before friction testing, to allow fluid to reflow into the contact interface and boundary lubricants to rearrange. Friction and adhesion of high-load-bearing joint regions were consistently lower than those of low-load-bearing regions. This investigation is the first to demonstrate the regional variation in the friction and adhesion properties of articular cartilage. Friction coefficient decreased with increasing contact pressure and decreasing equilibration time. Briefly unloading cartilage before the onset of sliding resulted in significantly lower friction and adhesion and a loss of the friction dependence on contact pressure, suggesting an enhancement of the cartilage tribological properties by trapped lubricants. The results of this study reveal significant differences in the friction and adhesion properties between high- and low-load-bearing joint regions and elucidate the role of trapped lubricants in cartilage tribology.     

Quantitative ultrasonic assessment for detecting microscopic cartilage damage in osteoarthritis

Osteoarthritis (OA) is one of the most prevalent chronic conditions. The histological cartilage changes in OA include surface erosion and irregularities, deep fissures, and alterations in the staining of the matrix. The reversibility of these chondral alterations is still under debate. It is expected that clinical and basic science studies will provide the clinician with new scientific information about the natural history and optimal treatment of OA at an early stage. However, a reliable method for detecting microscopic changes in early OA has not yet been established. We have developed a novel system for evaluating articular cartilage, in which the acoustic properties of the articular cartilage are measured by introducing an ultrasonic probe into the knee joint under arthroscopy. The purpose of this study was to assess microscopic cartilage damage in OA by using this cartilage evaluation system on collagenase-treated articular cartilage in vivo and in vitro. Ultrasonic echoes from articular cartilage were converted into a wavelet map by wavelet transformation. On the wavelet map, the maximum magnitude and echo duration were selected as quantitative indices. Using these indices, the articular cartilage was examined to elucidate the relationships of the ultrasonic analysis with biochemical, biomechanical and histological analyses. In the in vitro study, the maximum magnitude decreased as the duration of collagenase digestion increased. Correlations were observed between the maximum magnitude and the proteoglycan content from biochemical findings, and the maximum magnitude and the aggregate modulus from biomechanical findings. From the histological findings, matrix staining of the surface layer to a depth of 500 mum was closely related to the maximum magnitude. In the in vivo study, the maximum magnitude decreased with increasing duration of the collagenase injection. There was a significant correlation between the maximum magnitude and the aggregate modulus. The evaluation system therefore successfully detected microscopic changes in degenerated cartilage with the use of collagen-induced OA.     

Application of mesenchymal stem cell therapy for the treatment of osteoarthritis of the knee: A concise review

Osteoarthritis(OA) refers to a chronic joint disease characterized by degenerative changes of articular cartilage and secondary bone hyperplasia. Since articular cartilage has a special structure, namely the absence of blood vessels as well as the low conversion rate of chondrocytes in the cartilage matrix, the treatment faces numerous clinical challenges. Traditional OA treatment(e.g., arthroscopic debridement, microfracture, autologous or allogeneic cartilage transplantation,chondrocyte transplantation) is primarily symptomatic treatment and pain management, which cannot contribute to regenerating degenerated cartilage or reducing joint inflammation. Also, the generated mixed fibrous cartilage tissue is not the same as natural hyaline cartilage. Mesenchymal stem cells(MSCs) have turned into the most extensively explored new therapeutic drugs in cell-based OA treatment as a result of their ability to differentiate into chondrocytes and their immunomodulatory properties. In this study, the preliminary results of preclinical(OA animal model)/clinical trials regarding the effects of MSCs on cartilage repair of knee joints are briefly summarized, which lay a solid application basis for more and deeper clinical studies on cell-based OA treatment.     

In vivo tibiofemoral contact analysis using 3D MRI-based knee models

This paper quantified the motion of the tibiofemoral contact points during in vivo weight bearing flexion using MRI- based 3D knee models and two orthogonal fluoroscopic images. The contact points on the medial and lateral tibial plateau were calculated by finding the centroid of the intersection of the tibial and femoral cartilage layers and by using the bony geometry alone. Our results indicate that the medial femoral condyle remains in the central portion of the tibial plateau and the lateral condyle translates posteriorly with increasing flexion. Using the bony contact model increased the total translation of the medial and lateral condyles by 250 and 55%, respectively, compared to the cartilage contact model. These results suggest that using the bony geometry alone may not accurately represent the articular surfaces of the knee. Articular cartilage geometry may have to be used to accurately quantify tibiofemoral contact.     

Three-dimensional knee model: constrained by isometric ligament bundles and experimentally obtained tibio-femoral contacts

The purpose of this study is to investigate the effect of anterior portion of anterior cruciate ligament, posterior cruciate ligament, anterior and deep portions of medial collateral ligament and the tibio-femoral articular contacts on passive knee motion. A well-accepted reference model for a normal tibio-femoral joint is reconstructed from the literature. The proposed three-dimensional dynamic tibio-femoral model includes the isometric fascicles, ligament bundles and irregularly shaped medial-lateral contact surfaces. With the approach we aim to analyze bone shape and ligament related abnormalities of knee kinematics. The rotations, translations and the contact forces during passive knee flexion were compared against a reference model and the results were found in close accordance. This study demonstrated that isometric ligament bundles play an important role in understanding the femur shape from contact points on tibia. Femoral condyles are not necessarily spherical. The surgical treatments should consider both ligament bundle lengths and contact surface geometries to achieve a problem free knee kinematics after a knee surgery.