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PubMed1995

Experimental assessment by high frequency ultrasound of articular cartilage thickness and osteoarthritic changes.

OBJECTIVE: Osteoarthritis (OA) is characterized by progressive loss of articular cartilage in the involved joint. Accurate, reproducible measurement of the thickness of the cartilage in vivo, however, is difficult. Because development of an ultrasonic imaging device for intraarticular use is feasible and would permit acquisition of information that could complement the assessment of articular cartilage made at arthroscopy, we evaluated the efficacy of high frequency ultrasound in assessing the thickness and subsurface characteristics of normal and OA cartilage. METHODS: Blocks of human femoral cartilage and subchondral bone and chips of cartilage alone were examined in vitro with an experimental 25 MHz pulse-echo ultrasound scanner that portrayed cross sections of the cartilage as B-mode images. The gross and histologic appearance of the articular surface was used to identify specimens of unblemished, normal cartilage and OA cartilage. The speed of sound in cartilage, determined from measurements of cartilage thickness and sound transmission, was related to its biochemical composition. RESULTS: The speed of sound in normal cartilage (1658 +/- 185 m/s, n = 27) was greater than that in OA cartilage (1581 +/- 148 m/s, n = 40, p = 0.06), but was not related to the cartilage water content or the concentration of uronic acid or hydroxyproline. Images of normal cartilage showed a smooth echo band at the tissue surface with a hypoechoic matrix; in scans of fibrillated cartilage the width of this band was proportional to the depth of fibrillation (r = 0.78). Ultrasonic and histologic measurements of OA cartilage thickness were closely correlated (r = 0.87) and the mean coefficient of variation for repeated measurements was 2%. CONCLUSION: High frequency ultrasonic images obtained in vitro provide highly accurate and reproducible measurements of the thickness and subsurface characteristics of normal and OA articular cartilage.

Arthroscopy↗
PubMed1997

Bone morphogenetic protein 2 stimulates articular cartilage proteoglycan synthesis in vivo but does not counteract interleukin-1alpha effects on proteoglycan synthesis and content.

OBJECTIVE: To study the effect of bone morphogenetic protein 2 (BMP-2) on articular cartilage proteoglycan (PG) synthesis in vivo and to investigate whether BMP-2 is able to counteract the effects of interleukin-1 (IL-1) on articular cartilage PG synthesis and content. METHODS: BMP-2 alone or in combination with IL-1alpha was injected into murine knee joints. PG synthesis was measured by 35S-sulfate incorporation using an ex vivo method or autoradiography. Cartilage PG content was analyzed by measuring Safranin O staining intensity on histologic sections. RESULTS: BMP-2 appeared to be a potent stimulator of articular cartilage PG synthesis in vivo. However, BMP-2 was not able to counteract the deleterious effects of IL-1alpha on articular cartilage PG synthesis and content. In addition, intraarticular injections of BMP-2 induced chondrophytes. CONCLUSION: Although BMP-2 is a very potent stimulator of cartilage PG synthesis in vivo, the therapeutic applications of BMP-2 are limited due to the inability of BMP-2 to counteract the effects of IL-1 and the induction of chondrophytes.

Animals↗
PubMed1976

Polydispersity of human articular cartilage proteoglycan antigens.

Studies were undertaken to define more fully the antigenic properties of human articular cartilage proteoglycans, in anticipation of its potential contribution to alterations arising in diseased states and following cartilage transplantation. Proteoglycans, extracted from normal, adult articular cartilage by dissociative measures, were subjected to purification by cesium density gradient ultracentrifugation, under conditions facilitating both molecular aggregation and dissociation. A polydisperse population of reactive determinants was observed in immunodiffusion and hemagglutination inhibition systems, employing proteoglycan specific antisera on gradient fractions. Highly aggregated proteoglycan species appeared to contain potentially masked antigenic determinants, which were revealed after guanidine dissociation but not hyaluronidase digestion. Polyacrilamide disc gel electrophoresis in sodium dodecyl sulfate, in conjunction with disc elution experiments, confirmed proteoglycan antigenic polydispersity.

Adult↗
PubMed2005

[Expression of MMP-2 and MMP-9 in the tartrate-resistant acid phosphatase (TRAP)-positive mononuclear and multinucleated cells is correlated with articular cartilage damage].

AIM: To examine the role of matrix metalloproteinases(MMP) expressed by the tartrate-resistant acid phosphatase (TRAP)-positive mononuclear and multinucleated cells in articular cartilage damage. METHODS: C57BL/6 mice were immunized by injection of chicken type II(CII) collagen to construct the collagen-induced rheumatoid arthritis(CIA) model. The presence of TRAP positive cells in the synovial tissue of CIA mice was examined by enzyme histochemistry and expression of MMP-2,9 was assessed in TRAP positive cells by immunohistochemistry. RESULTS: Expression of MMP-2 (gelatinase A) and MMP-9 (gelatinase B) was detected in TRAP positive mononuclear and multinucleated cell. Quantity of TRAP positive cells and the destruction of articular cartilage had a positive correlation (r(s) =0.903, P<0.01). Expression of MMP-2 and MMP-9 in TRAP positive cells was also correlated significantly with the destruction of articular cartilage (r(s) =0.954, P<0.01). CONCLUSION: This study suggests that MMP-2 and MMP-9 expression by TRAP positive mononuclear and multinucleated cells are involved in articular cartilage destruction in CIA.

Acid Phosphatase↗
PubMed2002

Induction of advanced glycation end products and alterations of the tensile properties of articular cartilage.

OBJECTIVE: To determine whether increasing advanced glycation end products (AGEs) in bovine articular cartilage to levels present in aged human cartilage modulates the tensile biomechanical properties of the tissue. METHODS: Adult bovine articular cartilage samples were incubated in a buffer solution with ribose to induce the formation of AGEs or in a control solution. Portions of cartilage samples were assayed for biochemical indices of AGEs and tested to assess their tensile biomechanical properties, including stiffness, strength, and elongation at failure. RESULTS: Ribose treatment of cartilage induced increases in tissue fluorescence, absorbance, and pentosidine content (P < 0.001 for each comparison) by amounts similar to those that occur during aging in humans. Ribose treatment of cartilage also induced an increase in dynamic modulus (60% increase) and strength (35% increase), and a decrease (25% decrease) in strain (P < 0.001 for each comparison). CONCLUSION: The concomitant increase in AGEs and alteration of tensile properties of cartilage after ribose treatment suggest that aging-associated changes in AGEs have functional consequences for this tissue. The AGE-associated increases in strength and stiffness of cartilage may be beneficial by counteracting the decreases in these properties that are associated with degeneration. Conversely, the AGE-associated decrease in failure length, or increase in brittleness, together with increased stiffness may predispose cartilage to increased stress concentration, fracture, and aging-associated biomechanical dysfunction.

Animals↗
PubMed1997

Method of histomorphometric assessment of glycosaminoglycans in articular cartilage.

A method of image analysis has been developed for use in the semiquantitative histomorphometric assessment of glycosaminoglycans in articular cartilage stained with safranin O. The reliability of the methodology is reported along with its application to the assessment of articular cartilage in a model of osteoarthritis, i.e., transection of the anterior cruciate ligament in rabbits. With this system, specimens of normal and osteoarthritic articular cartilage were assessed histomorphometrically for the following parameters: total cartilage area, percentage of safranin O stained area, mean gray scale (average stain intensity), and gray scale index (the relative total amount of glycosaminoglycans). Reproducibility was established for 12 specimens of normal cartilage and found to have a SD of less than 8% of the mean for each parameter that was measured. Image analysis of osteoarthritic cartilage revealed each of the parameters, except for average stain intensity, to be significantly lower than that in control cartilage.

Animals↗
PubMed1989

Effects of intramuscular polysulfated glycosaminoglycan on chemical and physical defects in equine articular cartilage.

The effect of intramuscular polysulfated glycosaminoglycan (PSG) on repair of cartilage injury was evaluated in eight horses. In each horse, one middle carpal joint had both a partial-thickness and a full-thickness articular cartilage defect created. In the contralateral middle carpal joint, chemical articular cartilage injury was created by intra-articular injection of 50 mg sodium monoiodoacetate (MIA). Horses were divided into two groups for treatment. Group 1 horses (control) received an intramuscular injection of normal saline every four days for a total of seven injections starting seven days after cartilage injury. Group 2 horses received 500 mg of PSG intramuscularly every four days for seven treatments starting seven days after cartilage injury. Horses were maintained for 12 weeks. Horses were evaluated clinically, and their middle carpal joints were evaluated radiographically and arthroscopically at the end of the study. Joint tissues were also collected and examined microscopically. The only significant difference between groups was slightly greater matrix staining intensity for glycosaminoglycans in the radiate articular cartilage layer in MIA injected and PSG treated joints. Partial-thickness defects had not healed and the predominant repair tissue in full-thickness defects was fibrous tissue. It was concluded that using this joint injury model, 500 mg PSG administered intramuscularly had no effect on the healing of articular cartilage lesions, and minimal chondroprotective effect from chemically induced articular cartilage degeneration.

Animals↗
PubMed2006

Evaluation of the articular cartilage of the knee joint with vastly undersampled isotropic projection reconstruction steady-state free precession imaging.

PURPOSE: To determine the feasibility of the vastly undersampled isotropic projection reconstruction steady-state free precession (VIPR-SSFP) sequence for evaluating the articular cartilage of the knee joint. MATERIALS AND METHODS: A magnetic resonance (MR) examination of the knee was performed on 33 subjects using a GE 1.5T scanner and a phased-array extremity coil. VIPR-SSFP, proton density-weighted fast spin-echo (PD-FSE), fat-suppressed T2-weighted fast spin-echo (T2-FSE), and three-dimensional fat-suppressed spoiled gradient recall-echo (SPGR) sequences were performed on three asymptomatic volunteers and 10 patients with osteoarthritis of the knee joint. Signal-to-noise efficiency, and contrast-to-noise ratio (CNR) measurements were calculated for all sequences and compared with the use of paired t-tests. The VIPR-SSFP sequence was then performed on 20 consecutive patients who were undergoing a routine MR examination of the knee. RESULTS: The cartilage signal-to-noise efficiency of the VIPR-SSFP sequence was not significantly different from that of the PD-FSE and SPGR sequences. The cartilage signal-to-noise efficiency of the VIPR-SSFP sequence was significantly higher (P < 0.05) than that of the T2-FSE sequence. The VIPR-SSFP sequence produced images with significantly higher (P < 0.05) CNR between cartilage and synovial fluid than the PD-FSE and SPGR sequences, and significantly higher (P < 0.05) CNR between cartilage and subchondral bone than the T2-FSE sequence. The VIPR-SSFP sequence allowed excellent visualization of the articular cartilage of the knee joint in all subjects. All articular cartilage defects identified on the PD-FSE, T2-FSE, and SPGR images were well visualized on the VIPR-SSFP images. CONCLUSION: VIPR-SSFP images had high cartilage signal-to-noise efficiency and high CNR between cartilage and adjacent synovial fluid and subchondral bone; therefore, the sequence is well suited for evaluating the articular cartilage of the knee joint.

Adult↗
PubMed2005

Effects of radiofrequency energy on human articular cartilage: an analysis of 5 systems.

BACKGROUND: Previous radiofrequency work has not rigidly controlled energy application to the articular cartilage, giving uncertain results published to date. HYPOTHESIS: At minimal settings, radiofrequency probes cause cell death in measurable areas when applied to human articular cartilage. STUDY DESIGN: Controlled laboratory study. METHODS: Simulating operating room conditions, 5 commercially available radiofrequency probes were attached to a customized jig to standardize a minimal contact pressure of each probe tip to 2.0 g. Keeping all variables the same, probes were placed on specific points of fresh grade II human cartilage with treatment times of 1 and 3 seconds at the manufacturer's recommended settings. Grade III cartilage was also tested with a treatment time of 3 seconds, and grade II cartilage was studied with the probe held 1 mm off the cartilage surface. Cartilage was blindly analyzed by confocal microscopy using a live/dead cell viability assay to determine the extent of cell death. RESULTS: Radiofrequency probes produced significant cellular death in the form of a half-circle into the cartilage to variable depths. For treatment times of 1 and 3 seconds, cell death measurements ranged from 404 to 539 mum and 1034 to 1283 mum, respectively. One probe failed to show any effect, with minimal evidence of cell death or cartilage smoothing. When probes were kept a 1.0-mm distance above the cartilage, no cell death or cartilage smoothing was noted. Radiofrequency treatment of grade III cartilage penetrated to the subchondral bone. There was no statistically significant difference between the damage caused by monopolar and bipolar probes when tested under these rigidly controlled conditions. CONCLUSION: These results showed significant cellular death at these minimal conditions to the underlying chondrocytes with radiofrequency probes. Surgeons using this technology need to be aware of the power and dangerous potential these probes can have on articular cartilage.

Aged↗
PubMed1986

Presence of fibronectin in articular cartilage in two animal models of osteoarthritis.

Fibronectin content was determined in articular cartilage in a spontaneous dog model and in a meniscectomy rabbit model of osteoarthritis. Determination of the fibronectin content of urea extracts of articular cartilage by an enzyme linked immunosorbent assay (ELISA) disclosed that degenerated cartilage contained from 10- to 40-fold more fibronectin than normal cartilage. The finding that cartilage fibronectin content was increased in both animal models suggests that elevated cartilage fibronectin content is a general feature of the osteoarthritic process. Immunoperoxidase studies disclosed that fibronectin was distributed throughout the matrix in hyaluronidase treated normal and osteoarthritic cartilage from both animal models, but quantitative differences in fibronectin were not observed by these techniques.

Animals↗
PubMed2004

[Autologous chondrocyte transplantation for the treatment of articular cartilage defects inf the knee joint. Techniques and results].

BACKGROUND: Currently the use of autologous chondrocytes as a cartilage-repair procedure for the repair of injured articular cartilage of the knee joint, is recommended. METHODS: This review presents the technique of autologous chondrocyte transplantation (ACT) and their modifications as matrix-associated autologous chondrocyte transplantation (MACT). Beside the surgical procedure the experimental and clinical results are discussed. Furthermore the major complications and the indication guidelines are presented. RESULTS: Articular cartilage in adults has a poor ability to self-repair after a substantial injury. Surgical therapeutic efforts in treating cartilage defects have focused on bringing new cells capable of chondrogenesis into the lesions. With ACT good to excellent clinical results are seen in isolated posttraumatic lesions of the knee joint in the younger patient with the formation of hyaline-like repair tissue. The major complications are periosteal hypertrophy, delamination of the transplant, arthrofibrosis and transplant failure. The current limitations include osteoarthritic defects and higher patient age. CONCLUSION: With the right indication and operative technique ACT is an effective and save option for the treatment of large full thickness cartilage defect of the knee joint.

Cartilage Diseases↗
PubMed2004

Magnetic resonance evaluation of the interrelationship between articular cartilage and trabecular bone of the osteoarthritic knee.

OBJECTIVE: To use high-resolution magnetic resonance imaging (MRI) to determine the relationship between articular cartilage degeneration and trabecular bone changes of the femur, condyles and tibia in human knees with osteoarthritis (OA). METHODS: Subjects were divided into three groups: without OA (OA0), mild OA (OA1) and severe OA (OA2). Sagittal images of the knee (0.234 x 0.234mm2, 2-mm slice thickness) were obtained at 1.5T and used for calculating the volume and thickness of the femoral and tibial cartilage. Axial images (0.195 x 0.195mm2, 1-mm slice thickness) were used for calculating the trabecular bone structure parameters: apparent bone volume fraction, trabecular number, trabecular separation and trabecular thickness. RESULTS: Cartilage volume and thickness were less in patients with OA compared to normal controls (P<0.1). Articular cartilage thinning is associated with bone structure loss in the opposite femoral condyle (P<0.05). In varus OA, there were extensive correlations between medial tibia and medial femoral cartilage degeneration, and loss of bone structure in the lateral tibia and lateral condyle. Additional correlations existed between the compartmental differences (lateral minus medial) of cartilage thickness and bone structure. CONCLUSION: Degradation of articular cartilage within a compartment correlates with a loss of bone structure in the opposite compartment. The correlation between the (L-M) differences corroborates this relationship. Malalignment of the knee due to cartilage degeneration is associated with bone formation in the diseased condyle and bone resorption in the opposite compartment.

Age Factors↗
PubMed1996

Coordinated regulation of hyaluronan and aggrecan content in the articular cartilage of immobilized and exercised dogs.

OBJECTIVE: To study the influence of joint loading and immobilization on articular cartilage hyaluronan concentration and histological distribution in the knee joints of young dogs subjected to 11 weeks' immobilization by splinting, and 15 weeks' running exercise at a rate of 40 km/day. METHODS: The amount of hyaluronan in articular cartilage was determined by a competitive binding assay using a biotinylated hyaluronan binding complex (HABC) of aggrecan and link protein. Histologic sections were stained for the localization of hyaluronan with the HABC probe. Extracted proteoglycans were characterized by sodium dodecyl sulfate agarose gel electrophoresis. RESULTS: Immobilization significantly reduced the concentration of hyaluronan in all sites studied (tibial and femoral condyles, patellar surface of femur). The proportion of hyaluronan to total uronic acid (mainly from aggrecan) remained unchanged because of a concurrent decrease in aggrecan. The ratio of hyaluronan and aggrecan remained constant also in runners. The staining pattern of free hyaluronan in the tissue sections and the electrophoretic mobility of the extracted proteoglycans were not affected by the different loading regimes. CONCLUSION: Reduced joint loading due to splint immobilization significantly decreases both hyaluronan and aggrecan in the articular cartilage. The remarkably parallel changes in aggrecan and hyaluronan content suggest that joint loading exerts a coordinated influence on their metabolism.

Aggrecans↗
PubMed1998

Morphological and histochemical ageing changes in patellar articular cartilage of the rat.

The aim of this study was to investigate the variation in cartilage characteristics with age. Fresh-frozen cryostat sections of the patellar articular cartilage of the rat were used to demonstrate the enzyme activity of succinate dehydrogenase, lactate dehydrogenase, alkaline phosphatase, and acid phosphatase in the different layers and at different ages. Light microscopic techniques were used to analyse quantitative features such as thickness, cell density and the histological characteristics of the articular cartilage. The results indicate that cell density is significantly affected by age. Furthermore, it depends on the distance from the surface. The most marked decline in cell density occurred between months 3 and 6. The thickness of the articular cartilage also varies with age. The reduction in cartilage thickness was most striking between months 3 and 6. Differentiation into the histological layers is obvious after 3 months. Glycolytic enzymes were strongly reactive in all regions and at all ages, whereas aerobic activity declines with age. The metabolic and morphological changes in ageing cartilage contribute to trophic disorders and deterioration of the functional cartilaginous situation in adult cartilage.

Acid Phosphatase↗
PubMed2001

Biphasic poroviscoelastic simulation of the unconfined compression of articular cartilage: I--Simultaneous prediction of reaction force and lateral displacement.

This study investigated the ability of the linear biphasic poroelastic (BPE) model and the linear biphasic poroviscoelastic (BPVE) model to simultaneously predict the reaction force and lateral displacement exhibited by articular cartilage during stress relaxation in unconfined compression. Both models consider articular cartilage as a binary mixture of a porous incompressible solid phase and an incompressible inviscid fluid phase. The BPE model assumes the solid phase is elastic, while the BPVE model assumes the solid phase is viscoelastic. In addition, the efficacy of two additional models was also examined, i.e., the transversely isotropic BPE (TIBPE) model, which considers transverse isotropy of the solid matrix within the framework of the linear BPE model assumptions, and a linear viscoelastic solid (LVE) model, which assumes that the viscoelastic behavior of articular cartilage is solely governed by the intrinsic viscoelastic nature of the solid matrix, independent of the interstitial fluid flow. It was found that the BPE model was able to accurately account for the lateral displacement, but unable to fit the short-term reaction force data of all specimens tested. The TIBPE model was able to account for either the lateral displacement or the reaction force, but not both simultaneously. The LVE model was able to account for the complete reaction force, but unable to fit the lateral displacement measured experimentally. The BPVE model was able to completely account for both lateral displacement and reaction force for all specimens tested. These results suggest that both the fluid flow-dependent and fluid flow-independent viscoelastic mechanisms are essential for a complete simulation of the viscoelastic phenomena of articular cartilage.

Animals↗
PubMed2000

The organization of aggrecan in human articular cartilage. Evidence for age-related changes in the rate of aggregation of newly synthesized molecules.

The effect of age on the incorporation of newly synthesized aggrecan into the extracellular matrix of human articular cartilage was investigated. This property was measured in a pulse-chase explant culture system by determining the distribution of radiolabeled molecules ([(35)S]sulfate-labeled) between a nondissociating extract (phosphate-buffered saline), which extracts mainly nonaggregated macromolecules, and a dissociating extract (4 M GnHCl) containing mainly aggrecan that was complexed in situ with hyaluronan. The rate of incorporation of aggrecan into aggregates was much slower in mature cartilage than in tissue obtained from younger individuals. Furthermore, autoradiography showed that in mature cartilage, newly synthesized aggrecan is not transported from the pericellular environment within the first 18 h of chase culture, whereas in immature cartilage, it moves into the intercellular space during the same period, i.e. aggrecan is processed in the extracellular space very differently in young and adult articular cartilage. Experiments were also performed to show that the interaction of link protein with newly synthesized aggrecan depends on the maturity of the G(1) domain of aggrecan. This investigation has shown that the extracellular aggregation of aggrecan in adult human articular cartilage involves a number of intermediate structures. These have not been identified in the very young cartilage obtained from laboratory animals or in porcine and bovine articular cartilage obtained from the abattoir.

Age Factors↗
PubMed1998

Finite element formulation of biphasic poroviscoelastic model for articular cartilage.

The purpose of the present study was to develop a computationally efficient finite element model that could be useful for parametric analysis of the biphasic poroviscoelastic (BPVE) behavior of articular cartilage under various loading conditions. The articular cartilage was modeled as the BPVE mixture of a porous, linear viscoelastic, and incompressible solid and an inviscid and incompressible fluid. A finite element (FE) formulation of the BPVE model was developed using two different algorithms, the continuous and discrete spectrum relaxation functions for the viscoelasticity of the solid matrix. These algorithms were applied to the creep and stress relaxation responses to the confined compression of articular cartilage, and a comparison of their performances was made. It was found that the discrete spectrum algorithm significantly saved CPU time and memory, as compared to the continuous spectrum algorithm. The consistency analysis for the present FE formulation was performed in comparison with the IMSL, a commercially available numerical software package. It was found that the present FE formulation yielded consistent results in predicting model behavior, whereas the IMSL subroutine produced inconsistent results in the velocity field, and thereby in the strain calculation.

Algorithms↗
PubMed1998

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 (alpha=0.01), respectively, in the experimental compared to the contralateral joint. Articular cartilage thickness and stiffness were increased and decreased significantly (alpha=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.

Animals↗