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PubMed1999

Degradation and repair of articular cartilage.

Approximately 95,000 total knee replacements and 41,000 other surgical procedures to repair cartilaginous defects of the knee are performed annually in the United States (1). The response of normal articular cartilage to injury or arthritic degeneration is often a sub-optimal repair; the biochemical and mechanical properties of the new tissue differ from the native cartilage, resulting in inadequate or altered function. It is believed that the chondrocytes from the surrounding areas, although perhaps capable of some limited migration at the damaged site, are not able to proliferate and produce the macromolecules necessary to create an organized matrix characteristic of normal articular cartilage (2,3). Current therapeutic options for articular cartilage injuries and degeneration have resulted in repair tissue which may be hyaline-like, but does not approximate the durability and function of the normal articular surface. Numerous studies have been performed to increase our understanding of the normal repair process of articular cartilage and its limitations, and to devise methods and materials to regenerate the joint surface.

Animals↗
PubMed1987

Dermatan sulfate isomers in human articular cartilage characterized by high-performance liquid chromatography.

The Constituents of dermatan sulfate isomers in human articular cartilage were studied at the disaccharide level by high-performance liquid chromatography. Appreciable amounts of dermatan sulfate components, i.e., dermatan sulfate, chondroitin sulfate types G and B, could be detected after digestion with chondroitinases-B or -ABC. The oversulfated dermatan sulfate isomers were isolated only after digestion with chondroitinase-ABC but not with the AC-lyase. The dermatan sulfate isomers were found to be markedly increased in weight loading parts of articular cartilage. It is postulated that the dermatan sulfate isomers are formed as a result of the weight loading reaction, which may be responsible for the fibrosis of articular cartilage.

Adult↗
PubMed1975

Functional adaptation of the articular cartilage.

The effect of prolonged sparing and prolonged loading of the knee-joint of dogs on the glucosamine, sialic acid, sulphate and hydroxyproline contents of the articular cartilage was investigated. (a) In the articular cartilage of the spared leg the amount of sulphate decreased by 24.7%, while the sialic acid content remained unchanged. Hydroxyproline showed a slight decrease. (b) On increased loading, glucosamine augmented by 53% and sialic acid by 32.5%. No appreciable changes occurred in sulphate and hydroxyproline. It is concluded that an increased loading brings about accumulation of glycoproteins while the amount of sulphated glycosaminoglycans does not change appreciably; the glycoprotein content of the spared articular cartilage remains unchanged, whereas the chondroitin sulphate content decreases considerably.

Animals↗
PubMed1991

Arthritis induced immunologically with cationic amidated bovine serum albumin in the guinea pig. A morphological and biochemical study on the destruction of articular cartilage.

Arthritis was induced by injecting cationic amidated bovine serum albumin (aBSA) (pI approximately 9.2) into the knee joint of immunized guinea pigs and the mechanisms of articular cartilage destruction were studied morphologically and biochemically. Marked synovitis associated with polymorphonuclear leukocyte (PML) infiltration occurred within 1 day of the challenge. Articular cartilage infiltrated by PMLs was almost completely destroyed after 2 weeks. During the initial destructive process, proteoglycans were depleted from the cartilage and later collagen fibers disappeared. Granulation tissue growing in the inflamed synovium and bone marrow replaced the destroyed cartilage and joint cavity and formed fibrous scar tissue (fibrous ankylosis) by 8 weeks. Subsequently, the knee joints developed cartilagenous ankylosis by 12 weeks and finally bony ankylosis at 28 weeks. Autoradiography using 125I-aBSA and immunofluorescence studies for immunoglobulin (IgG) and complement (C3) demonstrated that the antigen is trapped in all zones of the articular cartilage and serves as a trigger for immune complex formation. Significantly increased neutral proteinase activities against substrates of proteoglycan subunits, [3H]carboxymethylated transferrin and L-pyroglutamyl-L-prolyl-L-valine-paranitroanilide were detected in homogenates of the synovium and cartilage from arthritic knee joints 1 and 2 weeks after induction. Inhibitor studies and pH curves suggested that the proteinase is leukocyte elastase. Measurable amounts of gelatinolytic activity, detected by activation with 4-aminophenylmercuric acetate and inhibited with EDTA, were also present in the same samples, but there was no detectable collagenase activity. The data on SDS-gelatin substrate gel showed that the proteinase is gelatinase derived from PMLs. These results suggest that in aBSA-induced arthritis, elastase and gelatinase from PMLs invading articular cartilage may play important roles in cartilage destruction.

Amino Acid Sequence↗
PubMed2003

Hand-held arthroscopic optical coherence tomography for in vivo high-resolution imaging of articular cartilage.

We describe a novel hand-held polarization optical coherence tomographic (OCT) probe that can be inserted into mammalian joints to permit real-time cross-sectional imaging of articular cartilage. The transverse and axial resolutions of the arthroscopic OCT device are roughly 17 and 10 microm, respectively. Two-dimensional cross-sectional images of cartilage tissue with 500 x 1000 pixels covering an area 6 mm in length and 2.8 mm in depth can be acquired at nearly five frames/s and with over 100 dB of dynamic range. Design of an OCT as a hand-held device capable of providing such an optical biopsy of articular cartilage allows eventual in vivo detection of microstructural changes in articular cartilage that are not apparent using conventional arthroscopic cameras. The OCT probe can be easily incorporated in a conventional arthroscope for cartilage site guidance. The optical arrangement in the OCT scope minimizes specular back-reflection of the probe end face and absorption of body fluid in the path and ensures in-focus OCT imaging when it is in contact with the cartilage specimen to be examined. Successful application of in vivo arthroscopy to porcine articular cartilage demonstrates sufficient resolution and practicality for use in human joints.

Animals↗
PubMed2005

The effect of a passive muscle stretching protocol on the articular cartilage.

OBJECTIVE: The aim of this study is to evaluate the articular cartilage alterations of rat ankles, after applying unilateral cyclic passive muscle stretching protocol in previously immobilized rats. METHODS: Twenty-two male albino rats divided into four groups, I--immobilized; IS--immobilized and stretched; S--stretched and C--control, were used in this experiment. The I and IS groups were immobilized for 4 weeks. In the muscle stretching protocol the treated ankle joint (groups IS and S) was manually full dorsal flexed 10 times for 60s with a 30s interval between each 60s period, 7 days a week for 3 weeks, to stretch the ankle plantar flexors muscle group. The right hind limb was free to move. At the end of the experiment, the ankles were removed, processed in paraffin and stained with hematoxylin-eosin and Safranin-O. Two blinded observers evaluated cellularity, chondrocyte cloning and Safranin-O staining through light microscopy. And a morphometric study was carried out using a hand count of chondrocyte cells and cartilage thickness measurement. RESULTS: No significant effect of solely muscle stretching concerning cellularity, chondrocyte cloning and Safranin-O staining parameters was detected. However, IS group presented a significantly higher reduction of proteoglycans content than the solely stretched and solely immobilized groups and the morphometric analysis showed significant cellularity increase without thickness alteration compared to control. CONCLUSIONS: These findings suggest that the stretching protocol used was harmful to the previously immobilized articular cartilage. However, the same stretching protocol did not harm the cartilage of non-immobilized groups.

Animals↗
PubMed1985

Singular perturbation analysis of the nonlinear, flow-dependent compressive stress relaxation behavior of articular cartilage.

The dominant mechanism giving rise to the viscoelastic response of articular cartilage during compression is the nonlinear diffusive interaction of the fluid and solid phases of the tissue as they flow relative to one another. The present study is concerned with the role of this interaction under uniaxial stress relaxation in compression. The model is a biphasic mixture of fluid and solid which incorporates the strain-dependent permeability found earlier from permeation experiments. When a ramp-displacement is imposed on the articular surface, simple, but accurate, asymptotic approximations are derived for the deformation and stress fields in the tissue for slow and moderately fast rates of compression. They are shown to agree very well with experiment and they provide a simple means for determining the material parameters. Moreover, they lead to important insights into the role of the flow-dependent viscoelastic nature of articular cartilage and other hydrated biological tissues.

Cartilage, Articular↗
PubMed2003

Modulation of endogenous osteogenic protein-1 (OP-1) by interleukin-1 in adult human articular cartilage.

BACKGROUND: Osteogenic protein-1 (OP-1, BMP-7) induces bone formation and cartilage growth. Since OP-1 is an anabolic factor expressed by human articular chondrocytes, we examined the response of endogenous OP-1 to interleukin-1beta (IL-1beta) in human articular cartilage. METHODS: Normal adult human articular cartilage explants were cultured for twenty-five days in the presence of medium only or were treated with a low dose (0.1 ng/mL) or high dose (1.0 ng/mL) of IL-1beta for forty-eight or ninety-six hours. Alternately, cartilage explants were cultured forty-eight hours with IL-1beta, followed by forty-eight hours in standard medium (recovery). Tissue was analyzed for OP-1 message (by means of the reverse transcriptase-polymerase chain reaction), protein (by means of enzyme-linked immunosorbent assay and Western blot analysis) and proteoglycan content. Medium was analyzed for released proteoglycans and OP-1. RESULTS: In the presence of medium, OP-1 maintained its steady state of mRNA and protein expression for as long as twenty-five days in culture. A low dose of IL-1beta led to some upregulation in message and a twofold (p < 0.02) increase in OP-1 protein characterized by enhanced processing and activation of OP-1. Removal of IL-1beta (recovery experiments) did not reverse its effect on OP-1 synthesis. A high dose of IL-1beta caused stronger upregulation of message and a twofold decrease in OP-1 protein content (p < 0.007) in the cartilage matrix. However, this decrease in the matrix was primarily due to a release of active OP-1 into the medium. After removal of the 1.0-ng/mL IL-1beta, the levels of OP-1 protein did not recover. CONCLUSION: The results of the present study indicate that human adult chondrocytes have an ability to respond anabolically to initial or early catabolic events through an upregulation of endogenous OP-1.

Aged↗
PubMed2003

Deformation of chondrocytes in articular cartilage under compressive load: a morphological study.

The main function of articular cartilage is to transmit load. The objective of this study was to describe the deformation of chondrocytes under static loading and its relation to collagen matrix deformation. Whole intact rabbit knee joints were loaded statically with either high or low magnitude and long or short duration. Specimens were cryopreserved while under load and prepared for morphological evaluation by field emission scanning electron microscopy. With this method an immediate preservation of the chondrocyte in its loaded state was possible. Static compression of articular cartilage produced a zone-specific deformation of chondrocyte shape, depending on the magnitude and duration of load. Under high-force and long-duration loading, the chondrocytes showed considerable deformation concomitant with the highly deformed collagen fibres. Chondrocyte deformation occurred mostly in the transitional and upper radial zones and less in the lower layers. There was no significant change of the chondrocyte shape in the tangential zone under high- or low-force short-duration loading. These results show that the chondrocytes undergo significant changes in shape ex vivo and that they are sensitive to differences in the magnitude and duration of loads being applied. Chondrocyte deformation is strongly linked to the deformation of the surrounding cartilage collagen matrix.

Adaptation, Physiological↗
PubMed1995

Imaging of immature articular cartilage using ultrasound backscatter microscopy at 50 MHz.

A high frequency sonographic technique-ultrasound backscatter microscopy-was used to visualize the subsurface structure of immature porcine articular cartilage from the knee joint. In 20-week-old pigs, all parts that were scanned, except the weight-bearing regions of the femoral condyles, demonstrated heterogeneous ultrasound backscatter characteristics within the articular cartilage. A trilaminar pattern consisting of hypoechoic, hyperechoic, and anechoic layers ranging from superficial to deep generally was observed, except in the weight-bearing regions of the femoral condyles, where a homogeneous anechoic pattern was seen. In the younger pigs (6 and 10 weeks old), the trilaminar backscatter pattern was not observed. Small, highly echogenic structures that correlated with vascular channels in histologic assessment were observed frequently in the cartilage of younger pigs, but they were seldom present in the cartilage of 20-week-old pigs. Structural details, such as disruption of the subchondral bone and presence of a thickened fibrous layer on the articular surface at the chondrosynovial junction, also were detected with the ultrasound backscatter microscope. We concluded that high frequency ultrasound can be used to visualize the subsurface structure of immature articular cartilage and some of its developmental changes. Further research is required to explain the mechanism underlying the observed backscatter characteristics of immature articular cartilage and to study its potential for the imaging of pathologic changes.

Animals↗
PubMed2005

Articular cartilage degeneration in post-collapse osteonecrosis of the femoral head. Radiographic staging, macroscopic grading, and histologic changes.

BACKGROUND: Osteonecrosis of the femoral head is a debilitating condition characterized by progressive degeneration of bone that eventually leads to collapse of the femoral head in the majority of patients. Femoral head-sparing procedures have been more successful in pre-collapse stages of osteonecrosis than in post-collapse stages, although some patients with early post-collapse disease have had no additional progression of the disorder. Nevertheless, the effects of collapse on the articular cartilage are not well understood, and radiographic staging of femoral head collapse does not address the condition of the articular cartilage. METHODS: In the current study, we investigated the relationship between the mechanical properties of post-collapse articular cartilage and the histologic findings and macroscopic grades of the articular cartilage from hips with stage-IV osteonecrosis, those with stage-V osteonecrosis, and those without osteonecrosis. RESULTS: The cartilage from both stage-IV and stage-V hips showed significant degeneration compared with the normal control cartilage, but there was no significant difference between the two stages. There was significant variability in the histologic and mechanical properties of these samples that correlated strongly with the gross appearance of the cartilage surface but not with the lesion size. CONCLUSIONS: These results suggest that articular cartilage that appears macroscopically normal may remain mechanically functional even in patients with large osteonecrotic lesions or a late radiographic stage of the disease.

Biomechanical Phenomena↗
PubMed2001

Evaluation of grades 3 and 4 chondromalacia of the knee using T2*-weighted 3D gradient-echo articular cartilage imaging.

OBJECTIVE: To determine the accuracy of T2*-weighted three-dimensional (3D) gradient-echo articular cartilage imaging in the identification of grades 3 and 4 chondromalacia of the knee. DESIGN AND PATIENTS: A retrospective evaluation of 80 patients who underwent both arthroscopic and MRI evaluation was performed. The 3D images were interpreted by one observer without knowledge of the surgical results. The medial and lateral femoral condyles, the medial and lateral tibial plateau, the patellar cartilage and trochlear groove were evaluated. MR cartilage images were considered positive if focal reduction of cartilage thickness was present (grade 3 chondromalacia) or if complete loss of cartilage was present (grade 4 chondromalacia). Comparison of the 3D MR results with the arthroscopic findings was performed. RESULTS: Eighty patients were included in the study group. A total of 480 articular cartilage sites were evaluated with MRI and arthroscopy. Results of MR identification of grades 3 and 4 chondromalacia, all sites combined, were: sensitivity 83%, specificity 97%, false negative rate 17%, false positive rate 3%, positive predictive value 87%, negative predictive value 95%, overall accuracy 93%. CONCLUSION: The results demonstrate that T2*-weighted 3D gradient-echo articular cartilage imaging can identify grades 3 and 4 chondromalacia of the knee.

Adolescent↗
PubMed2000

Role of nitric oxide in the inhibition of BMP-2-mediated stimulation of proteoglycan synthesis in articular cartilage.

OBJECTIVE: Bone morphogenetic protein-2 (BMP-2)-mediated stimulation of articular cartilage proteoglycan (PG) synthesis is suppressed in arthritic murine knee joints and by interleukin-1 (IL-1). The goal of this study was to investigate whether the gaseous mediator nitric oxide (NO) plays a crucial role in the inhibition of BMP-2 effects by IL-1. METHODS: Bone morphogenetic protein-2 alone or in combination with IL-1 was injected into the right knee joint of wild-type and NOS2 deficient C57BI/6x129/Sv mice. Proteoglycan synthesis was measured ex vivo by incorporation of 35S-sulfate on day 1, 2 and 3 after injection. To study the role of NO in the inhibition BMP-2-mediated stimulation of PG synthesis in arthritic joints, BMP-2 was injected intra-articularly in the joints of wild-type and NOS2 deficient mice with zymosan-induced arthritis. To check for NOS2 deficiency, NO production was measured in conditioned medium after challenge of patellae with surrounding tissue with IL-1. RESULTS: BMP-2 potently stimulated proteoglycan synthesis in articular cartilage of normal knees (up to 4-fold) but not in arthritic knees. Co-injection of BMP-2 with tumor necrosis factor alpha had no effect on BMP-2-mediated stimulation of PG synthesis but co-injection with IL-1 alpha resulted in a nearly total inhibition of BMP-2-mediated stimulation. In contrast, in NOS2 deficient mice IL-1 had no effect on BMP-2-mediated stimulation of PG synthesis. However, injection of BMP-2 into arthritic knee joints of NOS2 knock out mice did not result in significant stimulation of PG synthesis. CONCLUSIONS: In this study we show that NO plays a role in the inhibition of BMP-2-mediated stimulation of PG synthesis by IL-1. However, NO, or at least NOS2, plays no dominant role in the inhibition of BMP-2 effects in arthritic knee joints.

Animals↗
PubMed1980

Quasi-linear viscoelastic properties of normal articular cartilage.

A combined experimental and analytical approach was used to determine the history-dependent viscoelastic properties of normal articular cartilage in tension. Specimens along the surface split line direction, taken from the middle zone of articular cartilage were subjected to relaxation and cyclic tests. A quasi-linear viscoelastic theory proposed by Fung was used in combination with the experimental results to determine the nonlinear viscoelastic properties and the elastic stress-strain relationship of normal articular cartilage.

Animals↗
PubMedDate not supplied

Basic cell metabolism of articular cartilage. Manometric studies.

Basic metabolism generates energy by the anaerobic or aerobic metabolization of glucose. The articular cartilage obtains the substrate and oxygen from the synovial fluid. Their concentrations within the cartilage diminish with increasing proximity to the basal layer at the bone-cartilage boundary. The gradients depend upon the cell density and the consumption by the cells. The gradient of the partial oxygen pressure (PO2) could provide the conditions for the Pasteur effect, which, however, has not yet been clearly observed. Metabolic reactions of chondrocytes to positive or negative glucose gradient have not hitherto been examined, and are the object of the present study. The oxygen consumption (QO2) in the articular cartilage of pig femoral heads was measured manometrically (Warburg technique) in the absence of glucose and in its presence in concentrations of 1.25 to 10.0 mM. There was a close correlation between the QO2 and the concentration and consumption of glucose having the nature of a glucose-induced respiratory suppression (Crabtree effect). The consumption of glucose, which did not rise in proportion to its concentration, did not exceed 15.7 mumol/gdw/h. The maximum lactate production of 20 to 23 mumol/gdw/h was attained at 5 mM glucose and showed no further increase at higher substrate concentrations. This stoichiometric "lactate deficiency" means that the absorbed but not glycolyzed glucose is channeled into synthesizing and storage processes. In glucose-free incubation, despite aerobic conditions, lactate was utilized by the chondrocytes only at unphysiologically high concentrations greater than 10 mM. Potassium cyanide reduced the QO2 by only 80-90% as a sign of the activity of non-mitochondrial oxidases. With monoiodoacetate (MIA), respiration fell dramatically during the 4 h of substrate-free incubation. It can be concluded from the results that, under physiological conditions, the glucose level in the synovia reduces the consumption of oxygen in the well-glucose-supplied upper layer of the articular cartilage, thus allowing an oxidative compensation of the diminishing glycolysis in the basal zone. The Crabtree effect, which is demonstrated for the first time in chondrocytes, thus seems to have the role of an essential regulatory mechanism in the basic metabolism of the cartilage.

Animals↗
PubMed2004

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.

Animals↗
PubMed1998

Exercise protects against articular cartilage degeneration in the hamster.

OBJECTIVE: It has been reported that osteoarthritis can occur in hamsters. The present study was undertaken to determine the effects of exercise on the composition of articular cartilage and synovial fluid and on the development of cartilage degeneration in these animals. METHODS: Young (2.5-month-old) group-housed hamsters were compared with 5.5-month-old hamsters that had undergone 3 months of daily wheel running exercise (6-12 km/day) or 3 months of sedentary, individually housed living. The condition of the femoral condyles was determined by scanning electron microscopy in 12 exercising hamsters, 12 sedentary hamsters, and 6 of the young controls. The content of proteoglycan, hyaluronic acid, hydroxyproline, and proline in synovial fluid and patellar cartilage was measured. RESULTS: By scanning electron microscopy, the femoral articular cartilage was smooth and undulating in young controls and older exercising hamsters. In contrast, the femoral condyles were fibrillated in all 12 of the sedentary hamsters. There was no difference in the patellar cartilage collagen content between the 3 groups, but proteoglycan content and synthesis were lower in the patellar cartilage of the sedentary group. Synovial fluid volume was also decreased in the sedentary group compared with the young controls or the older exercising hamsters. CONCLUSION: A sedentary lifestyle in the hamster leads to a lower proteoglycan content in the cartilage and a lower synovial fluid volume. These changes are associated with cartilage fibrillation, pitting, and fissuring. Daily exercise prevents early cartilage degeneration and maintains normal articular cartilage.

Animals↗