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PubMed2001

Differentiation of chondrogenic precursor cells during the regeneration of articular cartilage.

OBJECTIVE: Full-thickness defects that penetrate articular cartilage are filled by fibrous, or fibrocartilaginous tissue and, to a very limited extent, also by hyaline cartilage. In rabbits, small full-thickness defects (to < or =3 mm in diameter) are capable of regenerating surfacing hyaline cartilage. However, chondrogenic differentiation does not occur in larger defects (> or =5 mm in diameter). We studied the involvement of fibroblast growth factor-2 (FGF-2) in the cartilaginous repair response in full-thickness defects of articular cartilage in vivo, and attempted to facilitate cartilaginous repair of the defects by the local administration of FGF-2. DESIGN: The right knee joint of male adolescent Japanese white rabbits was entered through a medial parapatellan approach, and the patella was dislocated laterally to expose the articular surface of the femoral trochlea. Full-thickness defects were created in the weight-bearing area of the femoral trochlea with a hand-drill (the 5-mm diameter defects in 80 rabbits and the 3-mm diameter defects in 40 rabbits). The animals were fitted with an osmotic pump connected to silastic medical grade tubing, and a length of the tubing about 5 mm long was introduced into the articular knee cavity. The 5-mm-diameter defects received FGF-2 (50 pg/h) or sterile saline via an osmotic pump for the initial 2 weeks. Five animals each were sacrificed after 1, 2, 4, 8, or 24 weeks after creation of defects. The 3-mm diameter defects received a neutralizing monoclonal antibody against FGF-2 (50 ng/h) or pre-immune mouse IgG (50 ng/h) for the initial 2 weeks. Five animals each were sacrificed after 2, 3, or 4 weeks after creation of defects. The distal portion of each femur was removed, fixed, decalcified, and embedded in paraffin for the subsequent histological analysis. Sections were cut in the transverse plane, and histologically examined. RESULTS: The administration of FGF-2 (50 pg/h) resulted in successful regeneration of articular cartilage and the subchondral bone within 8 weeks after creation of 5-mm diameter defects. In these defects, undifferentiated mesenchymal cells initiated chondrogenic differentiation coupled with replacement by subchondral bone, resulting in the resurfacing of the defects by hyaline cartilage and the recovery of subchondral bone up to the original bone-articular cartilage junction. In contrast, the administration of a neutralizing monoclonal antibody against FGF-2 clearly interfered with the action of endogenous FGF-2 in 3-mm diameter defects, which were filled with fibrous tissue. None of the antibody-treated defects were covered with cartilage. We then assessed the proliferative capacity of the undifferentiated mesenchymal cells in the defects by immunostaining the proliferating cell nuclear antigen (PCNA) at 1 week after creation of defects. The capacity of reparative tissue to form cartilage was well correlated with the occurrence in the defects of a cell population that was PCNA-positive, undifferentiated, and capable of self-renewal. CONCLUSIONS: The local administration of FGF-2 resulted in the successful resurfacing of large (5 mm in diameter) defects by hyaline cartilage. Prechondrogenic mesenchymal cells were the likely targets of FGF-2, which probably promoted the formation of cartilage by stimulating a selective expansion of chondroprogenitor cells. Thus, activation of FGF-2 signalling is critically important for the induction of cartilaginous repair response in full-thickness articular cartilage.

Animals↗

PubMedDate not supplied

Use of polarization-sensitive optical coherence tomography to determine the directional polarization sensitivity of articular cartilage and meniscus.

The directional polarization sensitivity of articular cartilage and meniscus is investigated by use of polarization-sensitive optical coherence tomography (PS-OCT) by varying the angle of incident illumination. Experimental results show that when the incident light is perpendicular to the tissue surface, normal articular cartilage demonstrates little polarization sensitivity, while meniscus demonstrates strong polarization sensitivity. Differences in optical phase retardation produced by articular cartilage and meniscus are observed when the incident angle of the scanning light beam is adjusted between 0 and 90 deg relative to the tissue surface. Directional polarization sensitivity of articular cartilage and meniscus as obtained by PS-OCT imaging using variations in the angle of incident illumination can be used to assess the orientation and organization of the collagen matrix of these tissues. The polarization sensitivity as evidenced by the Stokes vector and optical phase retardation images can be explained by the orientation of the angle of illumination relative to the unique structural organization of the collagen fibrils and fibers of articular cartilage and meniscus.

Animals↗

PubMed1996

Classification of articular cartilage lesions of the knee at arthroscopy.

Classification systems for articular cartilage lesions in the knee have been based primarily on the appearance and severity of damage to the articular cartilage. Each of these systems has deficiencies in the documentation of articular cartilage abnormalities. This article proposes a new classification system for articular cartilage lesions in the knee. This system incorporates multiple parameters such as appearance, depth of involvement, area, clinical stage, and location of the lesion. A four-sector-mapping system allowing precise documentation of the location of articular cartilage lesions in the femorotibial joint is proposed. One numerical category is used to assess severity of a chondral defect. The use of these categories allows the surgeon to accurately grade and locate damage to the articular cartilage and its relationship to other concomitant intra-articular abnormalities. The proposed classification system has proven advantageous in communicating complex findings.

Arthroscopy↗

PubMed1982

The effect of continuous mechanical pressure upon the turnover of articular cartilage proteoglycans in vitro.

Fragments of calf articular cartilage maintained in organ culture were subjected to continuous mechanical pressure applied by means of lead weights of differing sizes. Increasing the pressure from approximately 7.5-30 kgfcm-2 proportionately decreased the breakdown of proteoglycans as measured by the release of [35S]sulphate from prelabeled cartilage. The difference was observed as early as 24 hours after culture. During the first 24 hours after removal of a 30 kgfcm-2 pressure the release of [35S]sulphate was slightly greater than that of the nonweight-bearing controls and then subsequently returned to the level of the controls. Application of a mechanical pressure of 30 kgfcm-2 to calf articular cartilage reduced the incorporation of [35S]sulphate to about half the level of the nonweight-bearing controls. A pressure of 15 kgfcm-2 had no significant effect upon [35S]sulphate incorporation. The production of lactate by the cartilage under the influence of 30 kgfcm-2 for 4 days was not significantly different from that of nonweight-bearing controls indicating the retained viability of the tissue. The present study indicates that proteoglycan metabolism of calf articular cartilage in vitro is capable of responding rapidly to variations in applied load. The potential importance of this finding in terms of the functional demands of articular cartilage is apparent, and it can be speculated that a failure of this adaptability of the chondrocytes is an important factor in the etiology of degenerative joint disease.

Animals↗

PubMed1996

Distribution of hyaluronan in articular cartilage as probed by a biotinylated binding region of aggrecan.

The proportion of total tissue hyaluronan involved in interactions with aggrecan and link protein was estimated from extracts of canine knee articular cartilages using a biotinylated hyaluronan binding region-link protein complex (bHABC) of proteoglycan aggregate as a probe in an ELISA-like assay. Microscopic sections were stained with bHABC to reveal free hyaluronan in various sites and zones of the cartilages. Articular cartilage, cut into 20 microns-thick sections, was extracted with 4 M guanidinium chloride (GuCl). Aliquots of the extract (after removing GuCl) were assayed for hyaluronan, before and after papain digestion. The GuCl extraction residues were analyzed after solubilization by papain. It was found that 47-51% of total hyaluronan remained in the GuCl extraction residue, in contrast to the 8-15% of total proteoglycans. Analysis of the extract revealed that 24-50% of its hyaluronan was directly detectable with the probe, while 50-76% became available only after protease digestion. The extracellular matrix in cartilage sections was stained with the bHABC probe only in the superficial zone and the periphery of the articular surfaces, both sites known to have a relatively low proteoglycan concentration. Trypsin pretreatment of the sections enhanced the staining of the intermediate and deep zones, presumably by removing the steric obstruction caused by the chondroitin sulfate binding region of aggrecans. Enhanced matrix staining in these zones was also obtained by a limited digestion with chondroitinase ABC. The results indicate that a part of cartilage hyaluronan is free from endogenous binding proteins, such as aggrecan and link protein, but that the chondroitin sulfate-rich region of aggrecan inhibits its probing in intact tissue sections. Therefore, hyaluronan staining was more intense in cartilage areas with lower aggrecan content. A large proportion of hyaluronan resists GuCl extraction, even from 20-micrograms-thick tissue sections.

Aggrecans↗

PubMed1983

Characterization of latent and active forms of cartilage proteinases produced by normal immature rabbit articular cartilage in tissue culture.

Cultured tissue slices from normal immature rabbit articular cartilage released latent neutral metalloproteinases into serum-free medium. On activation with 4-aminophenylmercuric acetate, these metalloproteinases could degrade collagen, proteoglycan, and gelatin. Also produced were an acid proteinase with the properties of cathepsin D and an inhibitor of the neutral metalloproteinases. The appearance of both the proteinases and the inhibitor in the culture medium could be prevented by incubation of cultures with cycloheximide. The active and latent forms of the proteinases were characterized using Ultrogel AcA 54 chromatography.

Animals↗

PubMed1995

Rheumatoid synovial fibroblast adhesion to human articular cartilage. Enhancement by neutrophil proteases.

OBJECTIVE: To determine if preexposure of human articular cartilage to activated neutrophils alters rheumatoid synovial fibroblast adhesion to human articular cartilage. METHODS: Human articular cartilage was exposed to either activated neutrophils, interleukin-1, or supernatants obtained from activated neutrophils that had been treated with different protease inhibitors. Radiolabeled rheumatoid synovial fibroblasts were then incubated with the cartilage and the number of counts associated with the cartilage was determined. RESULTS: Pretreatment of human articular cartilage with either activated neutrophils or supernatants obtained from activated neutrophils enhanced subsequent rheumatoid synovial fibroblast adhesion. In contrast, interleukin-1 treatment of cartilage did not alter the adhesion of synovial fibroblasts. The enhanced adhesion could be attenuated by pretreatment of the neutrophil supernatants with either diisopropylfluorophosphonate or EGTA and almost completely abolished by using both inhibitors. CONCLUSION: This study demonstrates that adhesion of rheumatoid synovial fibroblasts to human articular cartilage can be enhanced by exposing the cartilage to proteases released by neutrophils. These results suggest that neutrophil products may play a role in enhancing adhesion of rheumatoid synovium to cartilage in vivo.

Adult↗

PubMed2006

Multinuclear NMR and microscopic MRI studies of the articular cartilage nanostructure.

Studies of the structure of articular cartilage by a number of NMR spectroscopic and imaging techniques are reviewed. Advantage is taken of the fact that the NMR investigations can be done non-invasively on the intact tissue and do not require sectioning, slicing and decalcification as in the case of electron microscopy. The different contributions to 1H T2 relaxation are described and it is pointed out that ignoring the biexponential behavior of the transverse relaxation can lead to serious errors in the proton density measurements and the T2 characterization of the articular cartilage. A way to slow the transverse relaxation and to minimize its angular dependence by the use of dipolar echo is described. 2H double quantum filtered spectroscopic MRI is a powerful technique to follow the orientation and density of the collagen fibers in articular cartilage. Using this technique, it was found that attachment of the cartilage to the bone has a stabilizing effect on the collagen matrix and that the hydroxyapatite in the calcified zone resides near the collagen fibers but does not contribute to their order. In response to mechanical pressure, it was shown that the collagen fibers flatten near the surface and become crimped near the bone. A number of NMR techniques have been described for the measurement of 23Na residual quadrupolar interaction. It was found that this can serve as a very sensitive measure of the depletion of proteoglycans. Finally, a combination of the above techniques was used to study a maturation of articular cartilage in pigs. The increased order and density of the collagen fibers from newborn to adult pigs revealed itself as a shortening of T2 and significant increase of the residual quadrupolar interaction of both 2H and 23Na nuclei.

Animals↗

PubMed1997

Aggrecan degradation in human intervertebral disc and articular cartilage.

Aggrecan degradation in human intervertebral disc and articular cartilage has been studied by using anti-neoepitope antibodies specific for the N-terminal degradation products generated by cleavage within the interglobular domain at the metalloproteinase and aggrecanase sites. Immunoblot analysis of extracts of annulus fibrosus, nucleus pulposus and articular cartilage demonstrated age-related patterns in the abundance of both degradation products. In all three tissues the metalloproteinase-generated fragment was present at very low levels in young individuals but increased in abundance with age. In the disc tissues, the abundance of this degradation product levelled off in the juvenile; for cartilage this occurred in early adulthood. Despite these temporal differences, the levels attained in adults were comparable for the three tissues. In contrast, the aggrecanase-generated degradation product exhibited tissue-specific differences in the variation of its abundance with age. Whereas this degradation product increased with age in annulus fibrosus and articular cartilage and had levelled off by adulthood, in nucleus pulposus it was present in greatest abundance in young individuals and decreased to very low levels with age. Examination of discs exhibiting various degrees of degeneration did not reveal any differences in the levels of the metalloproteinase and aggrecanase-generated cleavage products that could not be accounted for by differences in age. In adults the product of aggrecanase action was much more abundant in articular cartilage than in either of the disc tissues, despite the age-related increase also observed for annulus fibrosus. Analysis of tissue extracts with an antibody recognizing the G1 domain of aggrecan identified two major degradation products whose abundance and size were correlated with the fragments detected by the anti-neoepitope antibodies. Taken together, these results indicate that cleavage at the metalloproteinase and aggrecanase sites are quantitatively important events in aggrecan catabolism in both articular cartilage and intervertebral disc in vivo. Moreover the two enzyme systems act independently and exhibit differences in the degree to which they contribute to aggrecan degradation in these tissues.

Adolescent↗

PubMed2003

Dynamic measurement of internal solid displacement in articular cartilage using ultrasound backscatter.

Mechanics of articular cartilage can be represented using poroelastic theories where fluid and solid displacements are viscously coupled to create a time-dependent spatially heterogeneous behavior. In recent models of this tissue, finite element methods have been used to predict tissue deformation as a function of time for adult articular cartilage bearing a characteristic depth-dependent structure and composition. However, current experimental methods are limited in providing verification of these predictions. The current study presents an apparatus for imaging the radial displacement profile of cartilage in unconfined compression using an ultrasound technique called elastography. We acquired ultrasound A-scans across the lateral diameter of full-thickness cartilage disks containing a thin layer of underlying bone, during axial compression. Elastography was then applied to correlate temporally sequential A-scans to estimate the solid radial displacement profile in articular cartilage while it undergoes compression and stress-relaxation. Both time-dependent and depth-dependent solid radial displacement profiles were obtained with a precision better than 0.2 micro The results generally agree with predictions of poroelastic models, demonstrating lateral expansion with an effective Poisson's ratio just after completion of the compression phase of the mechanical tests reaching values from 0.18 to 0.4 (depending on compression speed), followed by contraction to lower values. A more restricted movement was observed at both the articular surface and near to the subchondral bone than at regions midway between these two locations.

Animals↗

PubMed1984

Studies on cryopreservation of articular cartilage chondrocytes.

UNLABELLED: We used cartilage cells isolated from bovine articular cartilage in experiments to: (1) determine the toxicity of cryopreservatives (glycerol and dimethyl sulphoxide) on chondrocytes, (2) evaluate methods of freezing chondrocytes to maximize viability after freezing, and (3) examine the biosynthetic activity of frozen and thawed chondrocytes in culture. Results showed that the toxicity of cryopreservatives to chondrocytes is dependent on the time and temperature of exposure as well as on the concentration of the cryopreservative. Maximum viability was obtained by a two-stage freezing procedure using a slow cooling period initially, with equilibration of the cells at -40 degrees Celsius before further rapid freezing to -80 degrees Celsius. After seventy-two hours in culture, chondrocytes that had been frozen using this protocol synthesized products that appeared by column chromatography to form proteoglycan aggregates. CLINICAL RELEVANCE: One of the reasons for failure of frozen osteochondral allografts is the deterioration of joint function after transplantation due to degeneration of the articular cartilage. An important factor in the survival of these cartilage grafts may be preservation of the viability of the chondrocytes during storage and maintenance of the cell's ability to function following storage. In this study we evaluated the ability to store chondrocytes in a frozen state with the aid of cryopreservatives. The results confirmed that chondrocytes will survive freezing and remain capable of functioning in the same manner as fresh chondrocytes. This suggests that chondrocytes in articular cartilage should be able to survive freezing. The pursuit of methods of preserving articular cartilage by freezing appears to be warranted.

Animals↗

PubMed2004

Biomechanical properties of human articular cartilage under compressive loads.

The function of articular cartilage is to support and distribute loads and to provide lubrication in the diarthrodial joints. Cartilage function is described by proper mechanical and rheological properties, strain and depth-dependent, which are not completely assessed. Unconfined and confined compression are commonly used to evaluate the Young's modulus (E) and the aggregate modulus (H(A)), respectively. The Poisson's ratio (nu) can be calculated indirectly from the equilibrium compression data, or using the biphasic indentation technique; it has recently been optically evaluated by using video microscopy during unconfined compression. The transient response of articular cartilage during confined compression depends on its permeability k; a constant value of k can be easily identified by a simple analytical model of confined compression tests, whereas more complex models or direct measurements (permeation tests) are needed to study the permeability dependence on deformation. A poroelastic finite element model of articular cartilage was developed for this purpose. The elastic parameters (E,nu) of the model were evaluated performing unconfined compression creep tests on human articular cartilage disks, whereas k was identified from the confined test response. Our combined experimental and computational method can be used to identify the parameters that define the permeability dependence on deformation, as a function of depth from articular surface.

Adaptation, Physiological↗

PubMedDate not supplied

Treatment options for articular cartilage defects of the knee.

The treatment of symptomatic articular cartilage defects of the knee has evolved tremendously in the past decade. Previously, there were limited treatment options available to patients who suffered from either partial-thickness or full-thickness cartilage lesions. Because articular cartilage has a limited capacity for healing, patients were often treated symptomatically until they became candidates for osteotomy or total joint replacement. Recently, both reparative and restorative procedures have been developed to address this significant source of morbidity in young active patients. Microfracture is a reparative technique that induces a healing response to occur in an area of articular cartilage damage. Osteochondral autografts and allografts in addition to autologous chondrocyte implantation are restorative techniques aimed at recreating a more normal articular surface. Both types of procedures have been developed to alleviate the symptoms associated with focal chondral defects, as well as limit their potential to progress to a diffuse degenerative arthritis. Treatment can vary depending on both cartilage defect and patient factors. This article summarizes the various treatment options that have recently become available.

Cartilage, Articular↗

PubMed1990

Development of an artificial articular cartilage.

We have attempted to develop an artificial articular cartilage on the basis of a new viewpoint of joint biomechanics in which lubrication and load-bearing mechanisms of natural and artificial joints are compared. We investigated poly(vinyl alcohol)-hydrogel (PVA-H) which has been recognized as a rubber-like gel and have improved the mechanical properties of this gel through a new synthetic process. In this article we report the biocompatibility and various mechanical properties of the new, improved PVA-H from the aspect of its usefulness as artificial articular cartilage. As regards the lubrication, we measured the change of thickness and fluid pressure of the gap formed between a glass plate and the specimen under loading and found that the PVA-H had a thicker fluid film under higher pressure than polyethylene (PE). The momentary stress transmitted through the specimen revealed that PVA-H had a lower peak stress and a longer duration of sustained stress than PE, suggesting a better damping effect. The wear factor of PVA-H was approximately five times as large as that of PE. Histological findings of the articular cartilage and synovial membranes around the PVA-H implanted for 8-52 weeks showed neither inflammatory nor degenerative changes. The PVA-H artificial articular cartilage could be attached to the underlying bone using an osteochondral composite material. Although there remain still some problems to solve, PVA-H seems to be a very interesting and promising material which meets the requirements of artificial articular cartilage.

Animals↗

PubMed2000

Development of artificial articular cartilage.

Attempts have been made to develop an artificial articular cartilage on the basis of a new viewpoint of joint biomechanics in which the lubrication and load-bearing mechanisms of natural and artificial joints are compared. Polyvinyl alcohol hydrogel (PVA-H), 'a rubber-like gel', was investigated as an artificial articular cartilage and the mechanical properties of this gel were improved through a new synthetic process. In this article the biocompatibility and various mechanical properties of the new improved PVA-H is reported from the perspective of its usefulness as an artificial articular cartilage. As regards lubrication, the changes in thickness and fluid pressure of the gap formed between a glass plate and the specimen under loading were measured and it was found that PVA-H had a thicker fluid film under higher pressures than polyethylene (PE) did. The momentary stress transmitted through the specimen revealed that PVA-H had a lower peak stress and a longer duration of sustained stress than PE, suggesting a better damping effect. The wear factor of PVA-H was approximately five times that of PE. Histological studies of the articular cartilage and synovial membranes around PVA-H implanted for 8-52 weeks showed neither inflammation nor degenerative changes. The artificial articular cartilage made from PVA-H could be attached to the underlying bone using a composite osteochondral device made from titanium fibre mesh. In the second phase of this work, the damage to the tibial articular surface after replacement of the femoral surface in dogs was studied. Pairs of implants made of alumina, titanium or PVA-H on titanium fibre mesh were inserted into the femoral condyles. The two hard materials caused marked pathological changes in the articular cartilage and menisci, but the hydrogel composite replacement caused minimal damage. The composite osteochondral device became rapidly attached to host bone by ingrowth into the supporting mesh. The clinical implications of the possible use of this material in articular resurfacing and joint replacement are discussed.

Aluminum Oxide↗

PubMedDate not supplied

The effects of methylprednisolone on normal and monocyte-conditioned medium-treated articular cartilage from dogs and horses.

OBJECTIVE: To study in vitro (1) the dose-response relationships between proteoglycan metabolism in normal and corticosteroid-treated articular cartilage; (2) long-term proteoglycan metabolism after treatment of articular cartilage with corticosteroids; and (3) the effect of corticosteroids on proteoglycan metabolism in articular cartilage treated with monocyte-conditioned medium (MCM). STUDY DESIGN: Equine and canine articular cartilage explants were treated with corticosteroids and MCM. Proteoglycan synthesis and degradation were measured by radioactive labeling in short-term culture, and the long-term effect of corticosteroid treatment on proteoglycan metabolism was studied in normal explants. ANIMALS: Two young cross-breed horses and 3 young Labrador retrievers. METHODS: Equine articular cartilage explants were incubated in medium containing methylprednisolone sodium succinate (MPS) at 0, .001, .01, .1, 1, and 10 mg/mL (final concentration) for 1 day and then in fresh medium without MPS. Proteoglycan synthesis was measured by incorporation of sodium [35S]sulfate at 1, 3, 7, 10, and 13 days after initial treatment with MPS. Proteoglycan release was measured from separate explants prelabeled with sodium [35S]sulfate and treated similarly. Equine articular cartilage explants were treated with equine MCM simultaneously with, and 24 hours before MPS, at 0, 0.01, 0.1, 1, or 5 mg/mL for 72 hours. Proteoglycan synthesis and degradation in these explants was compared. Proteoglycan synthesis and degradation were measured similarly in canine articular cartilage explants treated simultaneously with canine MCM and MPS at 0, 0.001, 0.01, 0.1, 1 and 10 mg/mL for 72 hours. Equine articular cartilage explants treated with 0, 0.01, 0.1, 1, and 5 mg/mL of MPS for 72 hours were evaluated histologically. RESULTS: Proteoglycan synthesis in normal equine articular cartilage was severely depressed by 10 mg/mL MPS for 24 hours, and proteoglycan synthesis failed to recover after 13 days of culture in medium without MPS. Cartilage treated with 5 mg/mL MPS had pyknotic chondrocyte nuclei and empty lacunae. Concentrations of 1 and 0.1 mg/mL MPS depressed proteoglycan synthesis in normal equine cartilage explants. For these 2 concentrations, proteoglycan synthesis recovered 2 days after MPS removal and increased significantly (P < .05) 7 days after treatment with MPS compared with controls without MPS. Concentrations of 0.001 and 0.01 mg/mL MPS did not significantly affect proteoglycan synthesis in normal equine cartilage explants. Cumulative proteoglycan loss over 13 days in culture from normal equine explants treated for 24 hours with different concentrations of MPS was not significantly different between treatment groups at any time point. MCM significantly depressed proteoglycan synthesis in both canine and equine articular cartilage explants and significantly increased proteoglycan release. These effects were prevented in the canine explants by simultaneous treatment with MPS at 1 and 0.1 mg/mL, and proteoglycan release induced by MCM in equine articular cartilage was inhibited by 1 mg/mL MPS. CONCLUSIONS: Concentrations of 1.0 and 0.1 mg/mL MPS alleviated articular cartilage degradation in MCM-treated articular cartilage in vitro. These concentrations of MPS in contact with normal cartilage explants for 24 hours are unlikely to be detrimental in the long term to proteoglycan synthesis. The response of articular cartilage to MPS was affected by treatment with MCM so that results of experiments with normal articular cartilage explants may not reflect results obtained with abnormal cartilage. CLINICAL RELEVANCE: It may be possible to find an intraarticular concentration of corticosteroid that protects articular cartilage against cytokine-induced matrix degradation yet not have prolonged or permanent detrimental effects on chondrocyte matrix synthesis.

Analysis of Variance↗

PubMed1995

Quantitation of articular cartilage using magnetic resonance imaging and three-dimensional reconstruction.

A quadrature knee coil was used in conjunction with a magnetic resonance imaging scanner for quantitation of test phantom volumes, ex vivo bovine cartilage thickness, and in vivo human articular cartilage volumes. Optimal magnetic resonance parameters were obtained by testing a series of spin-echo and gradient-echo pulse sequences to determine the sequence that provided the highest resolution of articular cartilage and best defined the cartilage interfaces with synovial fluid and subchondral bone. Extensive testing revealed that two sequences were required to define articular cartilage accurately: a spoiled gradient-echo sequence and a steady state free-precession sequence. Three-dimensional reconstruction and statistical analyses of test phantoms and of bovine and human cartilage images were performed. Differences between actual phantom volumes and three-dimensional measurements demonstrated that, as magnetic resonance slice thickness was increased, the measurement variability also increased (coefficient of variation ranging from 1.7 +/- 1.3% for 1.0 mm slice thickness to 22.7 +/- 1.9% for 3.0 mm slice thickness). When the phantom volume was greater than 1,800 mm3, the intraobserver, interobserver and interscan accuracies were greater than 97, 98, and 96%, respectively. This high degree of reproducibility pertained for the data on in vivo human cartilage data also. For experienced observers, the intraobserver and interobserver reproducibility were greater than 98 and 97%, respectively. The interscan reproducibility was greater than 98%. These data demonstrate that improved magnetic resonance pulse sequencing, in conjunction with three-dimensional reconstruction and measurement techniques, can accurately and reproducibly measure the volume of articular cartilage. Clinical application of this approach offers the potential for early diagnosis of osteoarthritis and for serial, noninvasive assessment of changes in articular cartilage volume in response to therapeutic modalities.

Adult↗

PubMed1990

Effects of tumor necrosis factor alpha and beta on resorption of human articular cartilage and production of plasminogen activator by human articular chondrocytes.

We examined the effects of recombinant human tumor necrosis factor (TNF) on human articular cartilage and chondrocytes in culture. Both TNF alpha and TNF beta stimulated cartilage matrix breakdown during prolonged culture and elevated the levels of plasminogen activator (PA) activity in both the supernatants and cell layers of cultured chondrocytes. Characterization of the PA activities by immunochemistry and by zymography following gel electrophoresis indicated that human chondrocytes produce both urokinase-type PA and tissue-type PA in response to TNF. The addition of both interleukin-1 and TNF alpha or TNF beta to chondrocyte cultures demonstrated a synergism between these cytokines in the generation of PA activity in the culture supernatants and cell layers. Our results suggest that both activated lymphocytes and monocytes may contribute to the cartilage destruction of inflammatory arthritis through their stimulation of chondrocytes with TNF beta and TNF alpha, respectively. Since PA is the only neutral proteinase reported to be elevated in TNF-stimulated chondrocyte cultures, it could have an important role in TNF-mediated cartilage destruction.

Cartilage, Articular↗