Proteoglycans and mechanical behavior of condylar cartilage.

Mandibular condylar cartilage functions as the load-bearing, shock-absorbing, lubricating material in temporomandibular joints. Little is known about the precise nature of the biomechanical characteristics of this fibro-cartilaginous tissue. We hypothesized that the fixed charge density associated with proteoglycans that introduces an osmotic pressure inside condylar cartilage will significantly increase the tissue's apparent stiffness. Micro-indentation creep tests were performed on porcine TMJ condylar cartilage at 5 different regions-anterior, posterior, medial, lateral, and central-in physiologic and hypertonic solutions. The intrinsic and apparent mechanical properties, including aggregate modulus, shear modulus, and permeability, were calculated by indentation test data and the biphasic theory. The apparent properties (with osmotic effect) were statistically higher than those of the intrinsic solid matrix (without osmotic effect). Regional variations in fixed charge density, permeability, and mechanical modulus were also calculated for condylar surface. The present results provide important quantitative data on the biomechanical properties of TMJ condylar cartilage.

Analysis of the dynamic permeation experiment with implication to cartilaginous tissue engineering.

In the present study, a I-D dynamic permeation of a monovalent electrolyte solution through a negatively charged-hydrated cartilaginous tissue is analyzed using the mechano-electrochemical theory developed by Lai et al. (1991) as the constitutive model for the tissue. The spatial distributions of stress, strain, fluid pressure, ion concentrations, electrical potential, ion and fluid fluxes within and across the tissue have been calculated. The dependencies of these mechanical, electrical and physicochemical responses on the tissue fixed charge density, with specified modulus, permeability, diffusion coefficients, and frequency and magnitude of pressure differential are determined. The results demonstrate that these mechanical, electrical and physicochemical fields within the tissue are intrinsically and nonlinearly coupled, and they all vary with time and depth within the tissue.

The influence of the fixed negative charges on mechanical and electrical behaviors of articular cartilage under unconfined compression.

Unconfined compression test has been frequently used to study the mechanical behaviors of articular cartilage, both theoretically and experimentally. It has also been used in explant and gel-cell-complex studies in tissue engineering. In biphasic and poroelastic theories, the effect of charges fixed on the proteoglycan macromolecules in articular cartilage is embodied in the apparent compressive Young's modulus and the apparent Poisson's ratio of the tissue, and the fluid pressure is considered to be the portion above the osmotic pressure. In order to understand how proteoglycan fixed charges might affect the mechanical behaviors of articular cartilage, and in order to predict the osmotic pressure and electric fields inside the tissue in this experimental configuration, it is necessary to use a model that explicitly takes into account the charged nature of the tissue and the flow of ions within its porous interstices. In this paper, we used a finite element model based on the triphasic theory to study how fixed charges in the porous-permeable soft tissue can modulate its mechanical and electrochemical responses under a step displacement in unconfined compression. The results from finite element calculations showed that: 1) A charged tissue always supports a larger load than an uncharged tissue of the same intrinsic elastic moduli. 2) The apparent Young's modulus (the ratio of the equilibrium axial stress to the axial strain) is always greater than the intrinsic Young's modulus of an uncharged tissue. 3) The apparent Poisson's ratio (the negative ratio of the lateral strain to the axial strain) is always larger than the intrinsic Poisson's ratio of an uncharged tissue. 4) Load support derives from three sources: intrinsic matrix stiffness, hydraulic pressure and osmotic pressure. Under the unconfined compression, the Donnan osmotic pressure can constitute between 13%-22% of the total load support at equilibrium. 5) During the stress-relaxation process following the initial instant of loading, the diffusion potential (due to the gradient of the fixed charge density and the associated gradient of ion concentrations) and the streaming potential (due to fluid convection) compete against each other. Within the physiological range of material parameters, the polarity of the electric potential depends on both the mechanical properties and the fixed charge density (FCD) of the tissue. For softer tissues, the diffusion effects dominate the electromechanical response, while for stiffer tissues, the streaming potential dominates this response. 6) Fixed charges do not affect the instantaneous strain field relative to the initial equilibrium state. However, there is a sudden increase in the fluid pressure above the initial equilibrium osmotic pressure. These new findings are relevant and necessary for the understanding of cartilage mechanics, cartilage biosynthesis, electromechanical signal transduction by chondrocytes, and tissue engineering.

Dynamic depth-dependent osmotic swelling and solute diffusion in articular cartilage monitored using real-time ultrasound.

The objective of this study was to investigate the feasibility of ultrasonic monitoring for the transient depth-dependent osmotic swelling and solute diffusion in normal and degenerated articular cartilage (artC) tissues. Full-thickness artC specimens were collected from fresh bovine patellae. The artC specimens were continuously monitored using a focused beam of 50 MHz ultrasound (US) during sequential changes of the bathing solution from 0.15 mol/L to 2 mol/L saline, 0.15 mol/L saline, 1 mg/mL trypsin solution, 0.15 mol/L saline, 2 mol/L saline and back to 0.15 mol/L saline. The transient displacements of US echoes from the artC tissues at different depths were used to represent the tissue deformation and the NaCl diffusion. The trypsin solution was used selectively to digest the proteoglycans in artC. It was demonstrated that high-frequency US was feasible for monitoring the transient osmotic swelling, solute transport and progressive degeneration of artC in real-time. Preliminary results showed that the normal bovine patellar artC shrank during the first several minutes and then recovered to its original state in approximately 1 h when the solution was changed from 0.15 mol/L to 2 mol/L saline. Degenerated artC showed neither shrinkage nor recovery during the same process. In addition, a dehydrated-hydrated artC specimen showed much stronger shrinkage and it resumed the original state when the solution was changed from 2 mol/L back to 0.15 mol/L saline. The diffusion of NaCl and the digestion process of proteoglycans induced by trypsin were also successfully monitored in real-time.

Osteochondral repair of primate knee femoral and patellar articular surfaces: implications for preventing post-traumatic osteoarthritis.

The risk of post-traumatic osteoarthritis following an intra-articular fracture is determined to large extent by the success or failure of osteochondral repair. To measure the efficacy of osteochondral repair in a primate and determine if osteochondral repair differs in the patella (PA) and the medial femoral condyle (FC) and if passive motion treatment affects osteochondral repair, we created 3.2 mm diameter 4.0 mm deep osteochondral defects of the articular surfaces of the PA and FC in both knees of twelve skeletally mature cynomolgus monkeys. Defects were treated with intermittent passive motion (IPM) or cast-immobilization (CI) for two weeks, followed by six weeks of ad libitum cage activity. We measured restoration of the articular surface, and the volume, composition, type II collagen concentration and in situ material properties of the repair tissue. The osteochondral repair response restored a mean of 56% of the FC and 34% of the PA articular surfaces and filled a mean of 68% of the chondral and 92% of the osseous defect volumes respectively. FC defect repair produced higher concentrations of hyaline cartilage (FC 83% vs. PA 52% in chondral defects and FC 26% vs. PA 14% in osseous defects) and type II collagen (FC 84% vs. PA 71% in chondral defects and FC 37% vs. PA 9% in osseous defects) than PA repair. IPM did not increase the volume of chondral or osseous repair tissue in PA or FC defects. In both PA and FC defects, IPM stimulated slightly greater expression of type II collagen in chondral repair tissue (IPM 81% vs. CI 74%); and, produced a higher concentration of hyaline repair tissue (IPM 62% vs. CI 42%), but IPM produced poorer restoration of PA articular surfaces (IPM 23% vs. CI 45%). Normal articular cartilage was stiffer, and had a larger Poisson's ratio and less permeability than repair cartilage. Overall Cl treated repair tissue was stiffer and less permeable than IPM treated repair tissue. The stiffness, Poisson's ratio and permeability of femoral condyle cast immobilized (FC CI) treated repair tissue most closely approached the normal values. The differences in osteochondral repair between FC and PA articular surfaces suggest that the mechanical environment strongly influences the quality of articular surface repair. Decreasing the risk of post-traumatic osteoarthritis following intra-articular fractures will depend on finding methods of promoting the osteochondral repair response including modifying the intra-articular biological and mechanical environments.

Templates of the cartilage layers of the patellofemoral joint and their use in the assessment of osteoarthritic cartilage damage.

OBJECTIVE: To develop a methodology for generating templates that represent the normal human patellofemoral joint (PFJ) topography and cartilage thickness, based on a statistical average of healthy joints. Also, to determine the cartilage thickness in the PFJs of patients with osteoarthritis (OA) and develop a methodology for comparing an individual patient's thickness maps to the normal templates in order to identify regions that are most likely to represent loss of cartilage thickness. DESIGN: The patella and femur surfaces of 14 non-arthritic human knee joints were quantified using either stereophotogrammetry or magnetic resonance imaging. The surfaces were aligned, scaled, and averaged to create articular topography templates. Cartilage thicknesses were measured across the surfaces and averaged to create maps of normal cartilage thickness distribution. In vivo thickness maps of articular layers from 33 joints with OA were also generated, and difference maps were created depicting discrepancies between the patients' cartilage thickness maps and the normative template. RESULTS: In the normative template, the surface-wide mean+/-SD (maximum) of the cartilage thickness was 2.2+/-0.4mm (3.7mm) and 3.3+/-0.6mm (4.6mm) for the femur and patella, respectively. It was demonstrated that difference maps could be used to identify regions of thinner-than-normal cartilage in patients with OA. Patients were shown to have statistically greater regions of thin cartilage over their articular layers than the normal joints. On average, patients showed deficits in cartilage thickness in the lateral facet of the patella, in the anterior medial and lateral condyles, and in the lateral trochlea of the femur. CONCLUSIONS: This technique can be useful for in vivo clinical evaluation of cartilage thinning in the osteoarthritic patellofemoral joint.

Electrical signals for chondrocytes in cartilage.

An important step toward understanding signal transduction mechanisms modulating cellular activities is the accurate predictions of the mechanical and electro-chemical environment of the cells in well-defined experimental configurations. Although electro-kinetic phenomena in cartilage are well known, few studies have focused on the electric field inside the tissue. In this paper, we present some of our recent calculations of the electric field inside a layer of cartilage (with and without cells) in an open circuit one-dimensional (1D) stress relaxation experiment. The electric field inside the tissue derives from the streaming effects (streaming potential) and the diffusion effect (diffusion potential). Our results show that, for realistic cartilage material parameters, due to deformation-induced inhomogeneity of the fixed charge density, the two potentials compete against each other. For softer tissue, the diffusion potential may dominate over the streaming potential and vice versa for stiffer tissue. These results demonstrate that for proper interpretation of the mechano-electrochemical signal transduction mechanisms, one must not ignore the diffusion potential.

The role of flow-independent viscoelasticity in the biphasic tensile and compressive responses of articular cartilage.

A long-standing challenge in the biomechanics of connective tissues (e.g., articular cartilage, ligament, tendon) has been the reported disparities between their tensile and compressive properties. In general, the intrinsic tensile properties of the solid matrices of these tissues are dictated by the collagen content and microstructural architecture, and the intrinsic compressive properties are dictated by their proteoglycan content and molecular organization as well as water content. These distinct materials give rise to a pronounced and experimentally well-documented nonlinear tension-compression stress-strain responses, as well as biphasic or intrinsic extracellular matrix viscoelastic responses. While many constitutive models of articular cartilage have captured one or more of these experimental responses, no single constitutive law has successfully described the uniaxial tensile and compressive responses of cartilage within the same framework. The objective of this study was to combine two previously proposed extensions of the biphasic theory of Mow et al. [1980, ASME J. Biomech. Eng., 102, pp. 73-84] to incorporate tension-compression nonlinearity as well as intrinsic viscoelasticity of the solid matrix of cartilage. The biphasic-conewise linear elastic model proposed by Soltz and Ateshian [2000, ASME J. Biomech. Eng., 122, pp. 576-586] and based on the bimodular stress-strain constitutive law introduced by Curnier et al. [1995, J. Elasticity, 37, pp. 1-38], as well as the biphasic poroviscoelastic model of Mak [1986, ASME J. Biomech. Eng., 108, pp. 123-130], which employs the quasi-linear viscoelastic model of Fung [1981, Biomechanics: Mechanical Properties of Living Tissues, Springer-Verlag, New York], were combined in a single model to analyze the response of cartilage to standard testing configurations. Results were compared to experimental data from the literature and it was found that a simultaneous prediction of compression and tension experiments of articular cartilage, under stress-relaxation and dynamic loading, can be achieved when properly taking into account both flow-dependent and flow-independent viscoelasticity effects, as well as tension-compression nonlinearity.

Patellofemoral stresses during open and closed kinetic chain exercises. An analysis using computer simulation.

Rehabilitation of the symptomatic patellofemoral joint aims to strengthen the quadriceps muscles while limiting stresses on the articular cartilage. Some investigators have advocated closed kinetic chain exercises, such as squats, because open kinetic chain exercises, such as leg extensions, have been suspected of placing supraphysiologic stresses on patellofemoral cartilage. We performed computer simulations on geometric data from five cadaveric knees to compare three types of open kinetic chain leg extension exercises (no external load on the ankle, 25-N ankle load, and 100-N ankle load) with closed kinetic chain knee-bend exercises in the range of 20 degrees to 90 degrees of flexion. The exercises were compared in terms of the quadriceps muscle forces, patellofemoral joint contact forces and stresses, and "benefit indices" (the ratio of the quadriceps muscle force to the contact stress). The study revealed that, throughout the entire flexion range, the open kinetic chain stresses were not supraphysiologic nor significantly higher than the closed kinetic chain exercise stresses. These findings are important for patients who have undergone an operation and may feel too unstable on their feet to do closed chain kinetic chain exercises. Open kinetic chain exercises at low flexion angles are also recommended for patients whose proximal patellar lesions preclude loading the patellofemoral joint in deeper flexion.

Constituents and pH changes in protein rich hyaluronan solution affect the biotribological properties of artificial articular joints.

The relationship between the coefficient of friction and pH value or protein constituents of lubricating fluid, together with viscosity, were studied within a bearing surface model for artificial joint, ultra-high molecular weight polyethylene (UHMWPE) against stainless steel (SUS), using a mechanical spectrometer. Four lubricants were tested in this study: sodium hyaluronate (HA), HA with albumin, HA with gamma-globulin, and HA with (L)alpha-dipalmitoyl phosphatidylcholine ((L)alpha-DPPC). The coefficient of friction between UHMWPE and SUS in HA with albumin or HA with gamma-globulin varied from 0.035 to 0.070 depending on angular velocity and pH. The coefficient of friction in HA or HA with (L)alpha-DPPC varied from 0.023 to 0.045 depending on angular velocity and pH. The variation in pH for HA with albumin had a large effect on the coefficient of friction at low range of angular velocity with viscosity independence. The variation in pH for HA with gamma-globulin had a large effect on the coefficient of friction with viscosity dependence at high angular velocity. The addition of (L)alpha-DPPC showed a small effect on the coefficient of friction at low angular velocity. This study confirms that the presence of albumin in the lubricant promotes pH dependence and viscosity independence of the tribological properties at low speed while the presence of globulin promotes pH and viscosity independence at low speed and promotes pH and viscosity dependence at high speed in the lubrication of UHMWPE against SUS. This study supports the clinical hypothesis that the effect of constituents and pH changes in periprosthetic fluid for the lubrication is a clue toward resolving many complications after total joint replacement.

An analysis of the effects of depth-dependent aggregate modulus on articular cartilage stress-relaxation behavior in compression.

An accurate description of the mechanical environment around chondrocytes embedded within their dense extracellular matrix (ECM) is essential for the study of mechano-signal transduction mechanism(s) in explant experiments. New methods have been developed to determine the inhomogeneous strain distribution throughout the depth of the ECM during compression (Schinagl et al., 1996, Annals of Biomedical Engineering 24, 500-512; Schinagl et al 1997. Journal of Orthopaedics Research 15, 499-506) and the corresponding depth-dependent aggregate modulus distribution (Wang and Mow, 1998. Transactions of the Orthopaedics Research Society 23, 484; Chen and Sah, 1999. Transactions of the Orthopaedics Research Society 24, 635). These results provide the motivation for the current investigation to assess the influence of tissue inhomogeneity on the chondrocyte milieu in situ, e.g. stress, strain, fluid velocity and pressure fields within articular cartilage. To describe this inhomogeneity, we adopted the finite deformation biphasic constitutive law developed by Holmes and Mow (1990 Journal of Biomechanics 23, 1145-1156). Our calculations show that the mechanical environment inside an inhomogeneous tissue differs significantly from that inside a homogeneous tissue. Furthermore, our results indicate that the need to incorporate an inhomogeneous aggregate modulus. or an anisotropy, into the biphasic theory to describe articular cartilage depends largely on the motivation for the study.

Biomechanical and topographic considerations for autologous osteochondral grafting in the knee.

This study characterizes the donor and recipient sites involved in osteochondral autograft surgery of the knee with respect to articular cartilage contact pressure, articular surface curvature, and cartilage thickness. Five cadaveric knees were tested in an open chain activity simulation and kinematic data were obtained at incremental knee flexion angles from 0 degrees to 110 degrees. Surface curvature, cartilage thickness, and contact pressure were determined using a stereophotogrammetry method. In all knees, the medial trochlea, intercondylar notch, and lateral trochlea demonstrated nonloadbearing regions. Donor sites from the distal-medial trochlea were totally nonloadbeadng. For the intercondylar notch, lateral trochlea, and proximal-medial trochlea, however, the nonloadbearing areas were small, and typical donor sites in these areas partially encroached into adjacent loadbearing areas. The lateral trochlea (77.1 m(-1)) was more highly curved than the typical recipient sites of the central trochlea (23.3 m(-1)), medial femoral condyle (46.8 m(-1)), and lateral femoral condyles (42.9 m(-1)) (P < 0.05). Overall, the donor sites had similar cartilage thickness (average, 2.1 mm) when compared with the typical recipient sites (average, 2.5 mm). The lateral trochlea and medial trochlea curvatures were found to better match the recipient sites on the femoral condyles, while the intercondylar notch better matched the recipient sites of the central trochlea. The distal-medial trochlea was found to have the advantage of being nonloadbearing. Preoperative planning using the data presented will assist in more conforming, congruent grafts, thereby maximizing biomechanical function.

Glenohumeral mechanics: a study of articular geometry, contact, and kinematics.

Stereophotogrammetry was used to investigate the functional relations between the articular surface geometry, contact patterns, and kinematics of the glenohumeral joint. Nine normal shoulder specimens were elevated in the scapular plane by using simulated muscle forces in neutral rotation (NR) and starting rotation (SR). Motion was quantified by analyzing the translations of the geometric centers of the humeral head cartilage and bone surfaces relative to the glenoid surface. In both NR and SR, the ranges of translations of the center of the humeral head cartilage surface were greatest in the inferior-superior direction (NR 2.0 +/- 0.7 mm, SR 2.9 +/- 1.2 mm). Results of this study also show that joints with less congruence of the articular surfaces exhibit larger translations, and elevation in SR yields greater translations than in NR. Kinematic analyses with the humeral head bone surface data yielded larger values of translation than analyses that used the cartilage surface data, suggesting that similar overestimations may occur in radiographic motion studies. Results of this study demonstrate that small translations of the humeral head center occurred in both SR and NR. The proximity of the origin of the helical axes to the geometric center of the humeral head articular surface confirmed that glenohumeral elevation is mainly rotation about this geometric center with small translations.

Effects of repetitive subfailure strains on the mechanical behavior of the inferior glenohumeral ligament.

The mechanical response of the inferior glenohumeral ligament to varying subfailure cyclic strains was studied in 33 fresh frozen human cadaver shoulders. The specimens were tested as bone-ligament-bone preparations representing the 3 regions of the inferior glenohumeral ligament (superior band and anterior and posterior axillary pouches) through use of uniaxial tensile cycles. After mechanical preconditioning, each specimen was subjected to 7 test segments, consisting of a baseline strain level L1 (400 cycles) alternating with either 1 (group A, 10 shoulders), 10 (group B, 13 shoulders), or 100 (group C, 10 shoulders) cycles at increasing levels (L2, L3, L4) of subfailure strain. Cycling to higher levels of subfailure strain (L2, L3, L4) produced dramatic declines in the peak load response of the inferior glenohumeral ligament for all specimens. The group of ligaments subjected to 100 cycles of higher subfailure strains demonstrated a significantly greater decrease in load response than the other 2 groups. Ligament elongation occurred with cyclic testing at subfailure strains for all 3 groups, averaging 4.6% +/- 2.0% for group A, 6.5% +/- 2.6% for group B, and 7.1% +/- 3.2% for group C. Recovery of length after an additional time of nearly 1 hour was minimal. The results from this study demonstrate that repetitive loading of the inferior glenohumeral ligament induces laxity in the ligament, as manifested in the peak load response and measured elongations. The mechanical response of the ligament is affected by both the magnitude of the cyclic strain and the frequency of loading at the higher strain levels. The residual length increase was observed in all of the specimens and appeared to be largely unrecoverable. This length increase may result from accumulated microdamage within the ligament substance, caused by the repetitively applied subfailure strains. The clinical relevance of the study is that this mechanism may contribute to the development of acquired glenohumeral instability, which is commonly seen in the shoulders of young athletes who participate in repetitive overhead sports activities.

Osteoarthritic changes in the biochemical composition of thumb carpometacarpal joint cartilage and correlation with biomechanical properties.

The biochemical composition and biomechanical properties of articular cartilage from 53 human thumb carpometacarpal (CMC) joints from cadavers aged 20 to 79 years were measured and studied in normal, mildly fibrillated, and advanced osteoarthritic (OA) joints. Statistical analyses were performed to determine the correlations between the compositional measures and biomechanical properties. For these CMC joint tissues we found that water content increased, proteoglycan content decreased, and collagen content per dry weight remained unaltered with progression of OA degeneration. We also found that with disease progression, as defined by an OA staging score, the aggregate modulus (ie, compressive stiffness) decreased, along with an unexpected moderate decrease in permeability. This latter finding appears to be specific to CMC cartilage degeneration since articular cartilage from knees and hips generally demonstrates an increase in permeability with water content and OA score. Correlations between biochemical composition and biomechanical properties were found to be stronger in joints with OA than in joints without OA. This finding suggests that OA changes in biochemical composition, relative to baseline normal values, directly affect the biomechanical properties of cartilage, even though the baseline compositional values themselves do not directly determine the magnitude of the biomechanical properties in normal tissue.

On the electric potentials inside a charged soft hydrated biological tissue: streaming potential versus diffusion potential.

The main objective of this study is to determine the nature of electric fields inside articular cartilage while accounting for the effects of both streaming potential and diffusion potential. Specifically, we solve two tissue mechano-electrochemical problems using the triphasic theories developed by Lai et al. (1991, ASME J. Biomech Eng., 113, pp. 245-258) and Gu et al. (1998, ASME J. Biomech. Eng., 120, pp. 169-180) (1) the steady one-dimensional permeation problem; and (2) the transient one-dimensional ramped-displacement, confined-compression, stress-relaxation problem (both in an open circuit condition) so as to be able to calculate the compressive strain, the electric potential, and the fixed charged density (FCD) inside cartilage. Our calculations show that in these two technically important problems, the diffusion potential effects compete against the flow-induced kinetic effects (streaming potential) for dominance of the electric potential inside the tissue. For softer tissues of similar FCD (i.e., lower aggregate modulus), the diffusion potential effects are enhanced when the tissue is being compressed (i.e., increasing its FCD in a nonuniform manner) either by direct compression or by drag-induced compaction; indeed, the diffusion potential effect may dominate over the streaming potential effect. The polarity of the electric potential field is in the same direction of interstitial fluid flow when streaming potential dominates, and in the opposite direction of fluid flow when diffusion potential dominates. For physiologically realistic articular cartilage material parameters, the polarity of electric potential across the tissue on the outside (surface to surface) may be opposite to the polarity across the tissue on the inside (surface to surface). Since the electromechanical signals that chondrocytes perceive in situ are the stresses, strains, pressures and the electric field generated inside the extracellular matrix when the tissue is deformed, the results from this study offer new challenges for the understanding of possible mechanisms that control chondrocyte biosyntheses.

The mechanical environment of the chondrocyte: a biphasic finite element model of cell-matrix interactions in articular cartilage.

Mechanical compression of the cartilage extracellular matrix has a significant effect on the metabolic activity of the chondrocytes. However, the relationship between the stress-strain and fluid-flow fields at the macroscopic "tissue" level and those at the microscopic "cellular" level are not fully understood. Based on the existing experimental data on the deformation behavior and biomechanical properties of articular cartilage and chondrocytes, a multi-scale biphasic finite element model was developed of the chondrocyte as a spheroidal inclusion embedded within the extracellular matrix of a cartilage explant. The mechanical environment at the cellular level was found to be time-varying and inhomogeneous, and the large difference ( approximately 3 orders of magnitude) in the elastic properties of the chondrocyte and those of the extracellular matrix results in stress concentrations at the cell-matrix border and a nearly two-fold increase in strain and dilatation (volume change) at the cellular level, as compared to the macroscopic level. The presence of a narrow "pericellular matrix" with different properties than that of the chondrocyte or extracellular matrix significantly altered the principal stress and strain magnitudes within the chondrocyte, suggesting a functional biomechanical role for the pericellular matrix. These findings suggest that even under simple compressive loading conditions, chondrocytes are subjected to a complex local mechanical environment consisting of tension, compression, shear, and fluid pressure. Knowledge of the local stress and strain fields in the extracellular matrix is an important step in the interpretation of studies of mechanical signal transduction in cartilage explant culture models.

Thenar insertion of abductor pollicis longus accessory tendons and thumb carpometacarpal osteoarthritis.

Although the etiology of osteoarthritis of the thumb carpometacarpal (CMC) joint remains unclear, some theories have focused on variations in the local anatomy of the abductor pollicis longus tendon insertion. This cadaver study of 68 specimens analyzed the relationship between a thenar insertion of an accessory abductor pollicis longus tendon and the presence and severity of thumb CMC osteoarthritis. The joint cartilage surfaces were visually graded for degenerative changes. Thirty-five of 68 specimens (51%) had a thenar insertion, most frequently inserting on either the abductor pollicis brevis or opponens pollicis fascia or muscle belly. No significant association between a thenar insertion and thumb CMC arthritis was observed. Conversely, increasing age was noted to have a significant association with degenerative joint disease. Thus, these findings indicate that a thenar slip of the abductor pollicis longus tendon does not correlate with the presence or severity of CMC osteoarthritis.

Hamstrings and iliotibial band forces affect knee kinematics and contact pattern.

Many clinical studies have emphasized the role of the hamstrings and the iliotibial band on knee mechanics, although few biomechanical studies have investigated it. This study therefore examined two hypotheses: (a) with loading of the hamstrings, the tibia translates posteriorly and rotates externally and the tibial contact pattern shifts anteriorly; furthermore, the changes in tibial kinematics alter patellar kinematics and contact; and (b) loading the iliotibial band alters the kinematics and contact pattern of the tibiofemoral joint similarly to loading the hamstrings, and loading the iliotibial band laterally translates the patella and its contact location. Five cadaveric knee specimens were tested with a specially designed knee-joint testing machine in an open-chain configuration. At various flexion angles, the knees were tested always with a quadriceps force but with and without a hamstrings force and with and without an iliotibial band force. The results support the first hypothesis. Hence, the hamstrings may be important anterior and rotational stabilizers of the tibia, a role similar to that of the anterior cruciate ligament. The results also support the second hypothesis, although the iliotibial band force had a smaller effect on the tibia than did the hamstrings force. Both forces also changed patellar kinematics and contact, demonstrating that these structures should also be considered during the clinical management of patellar disorders.

Mitogen-activated protein kinase signaling in bovine articular chondrocytes in response to fluid flow does not require calcium mobilization.

In the present study, the role of mitogen-activated protein kinases (MAPKs) in chondrocyte mechanotransduction was investigated. We hypothesized that MAPKs participate in fluid flow-induced chondrocyte mechanotransduction. To test our hypothesis, we studied cultured chondrocytes subjected to a well-defined mechanical stimulus generated with a laminar flow chamber. The extracellular signal-regulated kinases 1 and 2 (ERK1/2) were activated 1.6-3-fold after 5-15 min of fluid flow exposure corresponding to a chamber wall shear stress of 1.6 Pa. Activation of ERK1/2 was observed in the presence of both 10% FBS and 0.1% BSA, suggesting that the flow effects do not require serum agonists. Treatment with thapsigargin or EGTA had no significant effect on the ERK1/2 activation response to flow, suggesting that Ca2+ mobilization is not required for this response. To assess downstream effects of the activated MAPKs on transcription, flow studies were performed using chondrocytes transfected with a chimeric luciferase construct containing 2.4 kb of the promoter region along with exon 1 of the human aggrecan gene. Two-hour exposure of transfected chondrocytes to fluid flow significantly decreased aggrecan promoter activity by 40%. This response was blocked by treatment of chondrocytes with the MEK-1 inhibitor PD98059. These findings demonstrate that, under the conditions of the present study, fluid flow-induced signals activate the MEK-1/ERK signaling pathway in articular chondrocytes, leading to down-regulation of expression of the aggrecan gene.