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PubMed2006

Proposal for a nomenclature for magnetic resonance imaging based measures of articular cartilage in osteoarthritis.

OBJECTIVE: Magnetic resonance imaging (MRI) of articular cartilage has evolved to be an important tool in research on cartilage (patho)physiology and osteoarthritis (OA). MRI provides a wealth of novel and quantitative information, but there exists no commonly accepted terminology for reporting these metrics. The objective of this initiative was to propose a nomenclature for definitions and names to be used in scientific communications and to give recommendations as to which minimal methodological information should be provided when reporting MRI-based measures of articular cartilage in OA. METHODS: An international group of experts with direct experience in MRI measurement of cartilage morphology or composition reviewed the existing literature. Through an iterative process that included a meeting with a larger group of scientists and clinicians (December 2nd, 2004, Chicago, IL, USA), they discussed, refined, and proposed a nomenclature for MRI-based measures of articular cartilage in OA. RESULTS: The group proposes a nomenclature that describes: (1) the anatomical location and (2) the structural feature being measured, each name consisting of a metric variable combined with a tissue label. In addition, the group recommends minimal methodological information that should be described. CONCLUSIONS: Utilization of this nomenclature should facilitate communication within the scientific community. Further, the uniform adoption of comprehensive nomenclature to describe quantitative MRI- features of articular cartilage should strengthen epidemiological, clinical, and pharmacological studies in OA.

Cartilage, Articular↗
PubMed1999

Influence of site and age on biochemical characteristics of the collagen network of equine articular cartilage.

OBJECTIVE: To determine variations in biochemical characteristics of equine articular cartilage in relation to age and the degree of predisposition for osteochondral disease at a specific site. SAMPLE POPULATION: Articular cartilage specimens from 53 horses 4 to 30 years old. PROCEDURE: Healthy specimens were obtained from 2 locations on the proximal articular surface of the first phalanx that had different disease prevalences (site 1 at the mediodorsal margin and site 2 at the center of the medial cavity). Water, total collagen, and hydroxylysine contents and enzymatic (hydroxylysylpyridinoline [HP]) and nonenzymatic (pentosidine) crosslinking were determined at both sites. Differences between sites were analyzed by ANOVA (factors, site, and age), and age correlation was tested by Pearson's product-moment correlation analysis. Significance was set at P< 0.01. RESULTS: Correlation with age was not found for water, collagen, hydroxylysine contents, and enzymatic cross-linking. Nonenzymatic crosslinking was higher in older horses and was linearly related to age (r = 0.94). Water and collagen contents and HP and pentosidine crosslinks were significantly higher at site 1. Hydroxylysine content was significantly lower at site 1. CONCLUSIONS: Except for nonenzymatic glycation, the composition of articular cartilage collagen does not change significantly in adult horses. A significant topographic variation exists in biochemical characteristics of the articular cartilage collagen network in equine metacarpophalangeal joints. These differences may influence local biomechanical properties and, hence, susceptibility to osteochondral disease, as will greater pentosidine crosslinks in older horses that are likely to cause stiffer and more brittle cartilage.

Aging↗
PubMed2004

Tetrapolar measurement of electrical conductivity and thickness of articular cartilage.

A tetrapolar method to measure electrical conductivity of cartilage and bone, and to estimate the thickness of articular cartilage attached to bone, was developed. We determined the electrical conductivity of humeral head bovine articular cartilage and subchondral bone from a 1- to 2-year-old steer to be 1.14+/-0.11 S/m (mean+/-sd, n =11) and 0.306+/-0.034 S/m, (mean+/-sd, n =3), respectively. For a 4-year-old cow, articular cartilage and subchondral bone electrical conductivity were 0.88+/-0.08 S/m (mean+/-sd, n =9) and 0.179+/-0.046 S/m (mean+/-sd, n =3), respectively. Measurements on slices of cartilage taken from different distances from the articular surface of the steer did not reveal significant depth-dependence of electrical conductivity. We were able to estimate the thickness of articular cartilage with reasonable precision (<20% error) by injecting current from multiple electrode pairs with different inter-electrode distances. Requirements for the precision of this method to measure cartilage thickness include the presence of a distinct layer of calcified cartilage or bone with a much lower electrical conductivity than that of uncalcified articular cartilage, and the use of inter-electrode distances of the current injecting electrodes that are on the order of the cartilage thickness. These or similar methods present an attractive approach to the non-destructive determination of cartilage thickness, a parameter that is required in order to estimate functional properties of cartilage attached to bone, and evaluate the need for therapeutic interventions in arthritis.

Animals↗
PubMed2003

Induction of apoptosis of articular chondrocytes and suppression of articular cartilage proteoglycan synthesis by heat shock.

We investigated cellular and matrix responses of articular cartilage to heat shock. Rat articular cartilage was pretreated at 37 degrees C for 24 h before being exposed to 48 degrees C for 10 min and subsequently incubated at 37 degrees C for 1, 2, 4, 7, 10, and 14 days. Following heat shock, a terminal deoxynucleotidyl transferase nick end labeling assay showed that articular chondrocyte apoptosis appeared at day 1, peaked at day 7, and declined by day 14. Analysis by transmission electron microscopy confirmed that the chondrocytes had characteristic morphological features of apoptosis; immunohistochemical staining revealed that caspase-3 activity in chondrocytes increased, 3-B-3-positive articular chondrocytes decreased in number, and the expression of 3-B-3 native epitope in articular chondrocytes was reduced. Safranin-O staining revealed that depletion of proteoglycans in the matrix was not found in any group. Morphological and biochemical evidence from this study suggested that heat shock at 48 degrees C induced articular chondrocyte apoptosis and suppressed proteoglycan synthesis of articular cartilage in vitro. This study thus provides evidence of the onset of osteoarthritis induced by heat shock and a basis for choosing a temperature at which malignant bone tumor cells can be killed with minimal damage to articular cartilage.

Animals↗
PubMed1993

Alterations of proteoglycan synthesis in rabbit articular cartilage induced by intra-articular injection of papain.

In order to investigate the biochemical alteration of proteoglycan (PG) synthesis during cartilage repair, reversible destruction was induced by injecting papain into the knee joint cavity of rabbits. The PG synthesis in the cartilage was examined using Na2 35SO4 and high performance liquid chromatography (HPLC). PGs labeled with 35SO4(2-) (35S-PGs) were extracted from normal and papain-treated cartilage, and the amount of synthesis, ability to aggregate with hyaluronan (HA), and the composition of glycosaminoglycan and chondroitin sulfate isomer labeled with 35SO4(2-) (35S-GAG and 35S-CS isomer) were analyzed. Synthesis of 35S-PGs, especially those that were unable to aggregate with HA (nonaggregating 35S-PGs), increased in papain-treated cartilage compared with that in normal cartilage. The acceleration and qualitative change in PG synthesis in the papain-treated cartilage are considered to be responses to the supplementation of the loss of cartilage PGs induced by papain. The compositions of 35S-GAG and 35S-CS isomer of the nonaggregating 35S-PGs differed from those of 35S-PGs which were able to aggregate with HA (aggregating 35S-PGs) in the papain-treated cartilage as well as in the normal cartilage. However, the compositions of both nonaggregating and aggregating 35S-PGs in the papain-treated and normal cartilage were similar. These results indicate that most of the nonaggregating 35S-PGs in papain-treated cartilage have properties similar to those in normal cartilage and are not simple degradation products of aggregating 35S-PGs; they also suggest that the supplementary reaction for PG content in the cartilage during its repair process is not simple acceleration in PG turn-over but the enhancement of PG synthesis accompanied by alterations in aggregating ability and the compositions of GAG and CS isomer.

Animals↗
PubMed1990

Ultrastructural study of hip joint osteoarthritis. Scanning electron microscopic study of articular cartilage of femoral head.

The surface structure of four different articular cartilages of the femoral head was studied with scanning electron microscope in 12 cases of hip joint osteoarthritis. These articular cartilages were mink white, yellow, dusky red and hyperplastic and thickened. The osteoarthritic articular cartilage surface was uneven with puckerings of various height, width and orientation. The puckerings were covered with fibril network. The fibrils were exposed collagen fibrils and of different diameters. Wider fiber bundles without orientation were found on the fibril network. On the surface of the hyperplastic articular cartilage observed were many deep and oval spaces left behind after breakdown of the lacunae of cells in the clusters of articular chondrocytes. In the spaces, remnants of articular chondrocytes were seen.

Cartilage, Articular↗
PubMed1979

Effect of salicylate on proteoglycan metabolism in normal canine articular cartilage in vitro.

In osteoarthritis, diminished aggregation of articular cartilage proteoglycans affects tissue biomechanics. Since salicylates are commonly employed in treatment of osteoarthritis, we examined the effect of sodium salicylate on proteoglycan metabolism and aggregation in normal canine articular cartilage. At salicylate concentrations of 10(-3)M, 5 X 10(-3)M and 10(-2)M, net proteoglycan synthesis in normal canine articular cartilage was 73%, 42% and 16% respectively, of control levels. Catabolism of glycosaminoglycans in the presence of 10(-3)M salicylate (which corresponds to a serum salicylate level of 20-25 mg %) was the same as that in control cartilage, while higher concentrations of the drug increased the rate of degradation. The hydrodynamic size of newly synthesized proteoglycan aggregates and of disaggregated proteoglycans was unaffected by sodium salicylate.

Animals↗
PubMed2003

Toward an MRI-based method to measure non-uniform cartilage deformation: an MRI-cyclic loading apparatus system and steady-state cyclic displacement of articular cartilage under compressive loading.

Recent magnetic resonance imaging (MRI) techniques have shown potential for measuring non-uniform deformations throughout the volume (i.e. three-dimensional (3D) deformations) in small orthopedic tissues such as articular cartilage. However, to analyze cartilage deformation using MRI techniques, a system is required which can construct images from multiple acquisitions of MRI signals from the cartilage in both the underformed and deformed states. The objectives of the work reported in this article were to 1) design an apparatus that could apply highly repeatable cyclic compressive loads of 400 N and operate in the bore of an MRI scanner, 2) demonstrate that the apparatus and MRI scanner can be successfully integrated to observe 3D deformations in a phantom material, 3) use the apparatus to determine the load cycle necessary to achieve a steady-state deformation response in normal bovine articular cartilage samples using a flat-surfaced and nonporous indentor in unconfined compression. Composed of electronic and pneumatic components, the apparatus regulated pressure to a double-acting pneumatic cylinder so that (1) load-controlled compression cycles were applied to cartilage samples immersed in a saline bath, (2) loading and recovery periods within a cycle varied in time duration, and (3) load magnitude varied so that the stress applied to cartilage samples was within typical physiological ranges. In addition the apparatus allowed gating for MR image acquisition, and operation within the bore of an MRI scanner without creating image artifacts. The apparatus demonstrated high repeatability in load application with a standard deviation of 1.8% of the mean 400 N load applied. When the apparatus was integrated with an MRI scanner programmed with appropriate pulse sequences, images of a phantom material in both the underformed and deformed states were constructed by assembling data acquired through multiple signal acquisitions. Additionally, the number of cycles to reach a steady-state response in normal bovine articular cartilage was 49 for a total cycle duration of 5 seconds, but decreased to 33 and 27 for increasing total cycle durations of 10 and 15 seconds, respectively. Once the steady-state response was achieved, 95% of all displacements were within +/- 7.42 microns of the mean displacement, indicating that the displacement response to the cyclic loads was highly repeatable. With this performance, the MRI-loading apparatus system meets the requirements to create images of articular cartilage from which 3D deformation can be determined.

Adaptation, Physiological↗
PubMed1987

Use of cultured embryonal chick epiphyseal chondrocytes as grafts for defects in chick articular cartilage.

Full-thickness defects in articular cartilage were repaired with cultured homologous embryonic chick epiphyseal chondrocytes embedded in a biological resorbable immobilization vehicle (BRIV). This graft was successfully transplanted in mechanically induced defects in the surface of condylar articular cartilage of the tibiotarsal joint of four-month-old roosters. Healing of the defects was observed macroscopically, histologically, and histochemically and with the use of biochemical analyses for six months. Chondrocyte proliferation was seen 48 hours after implantation, and a hyaline cartilage matrix surrounding the cells was present two weeks later. Within eight weeks, the defects were completely filled with hyaline cartilage, which integrated smoothly with the neighboring cartilage without the formation of fibrous tissue at the interface. The cell content and rate of proteoglycan synthesis remained high for four months, then declined slowly to the level of the surrounding cartilage. Six months after transplantation, the cartilaginous tissue in the wound at levels below the ossification front showed penetration by vascular elements and young bone trabeculae at the margins of the reparative tissue. No signs of immunogenic rejection of the implants were observed. These results may be related to the employment of a capable source of cells, i.e., cultured chondrocytes characterized by a high mitotic rate and an early stage of development. The transplanted cells grew well and maintained their initial rate of proliferation, with definite maturation and transformation. The resulting cartilage was structurally reorganized according to the host pattern and under the influence of multitudinous environmental conditions. The articular zone preserved its cartilaginous phenotype, whereas the subchondral regions were transformed into bone.

Animals↗
PubMed2001

Articular cartilage repair using a tissue-engineered cartilage-like implant: an animal study.

OBJECTIVE: Because articular cartilage has limited ability to repair itself, treatment of (osteo)chondral lesions remains a clinical challenge. We aimed to evaluate how well a tissue-engineered cartilage-like implant, derived from chondrocytes cultured in a novel patented, scaffold-free bioreactor system, would perform in minipig knees with chondral, superficial osteochondral, and full-thickness articular defects. DESIGN: For in vitro implant preparation, we used full-thickness porcine articular cartilage and digested chondrocytes. Bioreactors were seeded with 20x10(6) cells and incubated for 3 weeks. Subsequent to culture, tissue cartilage-like implants were divided for assessment of viability, formaldehyde-fixed and processed by standard histological methods. Some samples were also prepared for electron microscopy (TEM). Proteoglycans and collagens were identified and quantified by SDS-PAGE gels. For in vivo studies in adult minipigs, medial parapatellar arthrotomy was performed unilaterally. Three types of defects were created mechanically in the patellar groove of the femoral condyle. Tissue-engineered cartilage-like implants were placed using press-fit fixation, without supplementary fixation devices. Control defects were not grafted. Animals could bear full weight with an unlimited range of motion. At 4 and 24 weeks postsurgery, explanted knees were assessed using the modified ICRS classification for cartilage repair. RESULTS: After 3-4 weeks of bioreactor incubation, cultured chondrocytes developed a 700-microm- to 1-mm-thick cartilage-like tissue. Cell density was similar to that of fetal cartilage, and cells stained strongly for Alcian blue and safranin O. The percentage of viable cells remained nearly constant (approximately 90%). Collagen content was similar to that of articular cartilage, as shown by SDS-PAGE. At explantation, the gross morphological appearance of grafted defects appeared like normal cartilage, whereas controls showed irregular fibrous tissue covering the defect. Improved histologic appearance was maintained for 6 months postoperatively. Although defects were not always perfectly level upon implantation at explanation the implant level matched native cartilage levels with no tissue hypertrophy. Once in place, implants remodelled to tissues with decreased cell density and a columnar organization. CONCLUSIONS: Repair of cartilage defects with a tissue-engineered implant yielded a consistent gross cartilage repair with a matrix predominantly composed of type II collagen up to 6 months after implantation. This initial result holds promise for the use of this unique bioreactor/tissue-engineered implant in humans.

Animals↗
PubMed1999

Validity of histopathological grading of articular cartilage from osteoarthritic knee joints.

OBJECTIVES: To determine the validity of the histological-histochemical grading system (HHGS) for osteoarthritic (OA) articular cartilage. METHODS: Human articular cartilage was obtained from macroscopically normal (n = 13) and OA (n = 21) knee joints. Sections of central and peripheral regions of normal samples were produced. Sections of regions containing severe, moderate, and mild OA changes were produced from each OA sample. A total of 89 sections were graded by means of the HHGS (0-14) twice by three observers. RESULTS: Average scores for regions designated severe (8.64) and moderate (5.83) OA were less than the expected (10-14 and 6-9, respectively) according to the HHGS, whereas average scores for the region designated mild (5.29) OA and central and peripheral regions (2.19) of normal cartilage were higher than expected (2-5 and 0-1, respectively). The HHGS was capable of differentiating between articular cartilage from macroscopically normal and OA joints and between the region designated severe OA and other regions. However, the HHGS did not adequately differentiate between regions designated mild and moderate OA. Values for sensitivity, specificity, and efficiency for all regions varied considerably. CONCLUSION: The HHGS is valid for normal and severe OA cartilage, but does not permit distinction between mild and moderate OA changes in articular cartilage.

Adolescent↗
PubMed1979

Reconstruction of articular cartilage with free autologous perichondrial grafts. An experimental study in rabbits.

An experimental study in adult rabbits has been performed to find out whether the cartilage forming capacity of the perichondrium could be utilized in reconstruction of articular cartilage. The normal articular cartilage of the glenoid surface of the humero-scapular joint was completely removed. Auricular perichondrium was grafted to cover the exposed bony surface with the active chondrogenic layer of the perichondrial graft facing the joint cavity. The joint was not immobilized but the operated limb was amputated at wrist level to avoid weight bearing. The animals were sacrificed at different time intervals ranging from 1 to 17 weeks. In 12 out of 14 grafted rabbits regeneration of cartilage occurred. In 6 of 10 control cases where no perichondrium was grafted to cover the resected surface no cartilage was found. In the other 4, only small areas of mature cartilage were seen, probably remnants of the original articular cartilage.

Amputation, Surgical↗
PubMed1998

Human urinary trypsin inhibitor inhibits the activation of pro-matrix metalloproteinases and proteoglycans release in rabbit articular cartilage.

Treatment of primary cultured chondrocytes from rabbit articular cartilage with interleukin-1 (IL-1)alpha and plasminogen induced the production of pro-matrix metalloproteinase 1 (proMMP-1/interstitial collagenase), proMMP-3 (stromelysin 1) and proMMP-9 (gelatinase B), as well as their active forms. Human urinary trypsin inhibitor (UTI), a multipotent inhibitor of serine proteases, including plasmin inhibited the activation of proMMP-1, proMMP-3 and proMMP-9 when added to the culture medium together with IL-1alpha and plasminogen, in a dose-dependent manner. Moreover, UTI inhibited the release of proteoglycans induced by IL-1alpha and plasminogen from rabbit articular cartilage explants. These findings strongly suggest that UTI inhibits the destruction of articular cartilage induced by plasmin and/or MMPs. Thus, UTI probably exert an anti-osteoarthritic action via inactivation of proMMPs.

Animals↗
PubMed2004

The correspondence between equilibrium biphasic and triphasic material properties in mixture models of articular cartilage.

Mixture models have been successfully used to describe the response of articular cartilage to various loading conditions. Mow et al. (J. Biomech. Eng. 102 (1980) 73) formulated a biphasic mixture model of articular cartilage where the collagen-proteoglycan matrix is modeled as an intrinsically incompressible porous-permeable solid matrix, and the interstitial fluid is modeled as an incompressible fluid. Lai et al. (J. Biomech. Eng. 113 (1991) 245) proposed a triphasic model of articular cartilage as an extension of their biphasic theory, where negatively charged proteoglycans are modeled to be fixed to the solid matrix, and monovalent ions in the interstitial fluid are modeled as additional fluid phases. Since both models co-exist in the cartilage literature, it is useful to show how the measured properties of articular cartilage (the confined and unconfined compressive and tensile moduli, the compressive and tensile Poisson's ratios, and the shear modulus) relate to both theories. In this study, closed-form expressions are presented that relate biphasic and triphasic material properties in tension, compression and shear. These expressions are then compared to experimental findings in the literature to provide greater insight into the measured properties of articular cartilage as a function of bathing solutions salt concentrations and proteoglycan fixed-charge density.

Animals↗
PubMed1997

Triple quantum sodium imaging of articular cartilage.

Triple quantum (TQ) sodium imaging of bovine articular cartilage is presented. True triple quantum imaging sequence was modified to incorporate asymmetric echo acquisition. Triple quantum signal expression in the presence of residual quadrupolar interaction is presented. The filtering capability of the sequence is first demonstrated on an agarose phantom. Both single and triple quantum images of articular cartilage are compared. The TQ image shows non-zero signal intensity solely from cartilage, indicating complete suppression of signals from bone marrow and saline. The advantages of TQ imaging of articular cartilage, its feasibility in in vivo situations and further improvements in SNR are described.

Animals↗
PubMed1982

Factors influencing articular cartilage wear in vitro.

The in vitro wear of articular cartilage in oscillating and impulsively loaded bovine metatarsophalangeal joints was studied. Articular cartilage scarification had little effect on cartilage wear, but stiffening of the subchondral bone with methyl methacrylate greatly increased the rate of cartilage loss, whether or not it had previously been scarified. Glutaraldehyde treatment of articular cartilage for 30 minutes decreased is wear rate. Guanidinium chloride extraction of the cartilage before wear testing caused it to peel off its subchondral bed. This effect could be spared by prior glutaraldehyde fixation.

Aging↗
PubMedDate not supplied

Force-mediated dissociation of proteoglycan aggregate in articular cartilage.

Proteoglycan aggregate is the primary component in articular cartilage responsible for resisting compressive loading. It consists of a core molecule of hyaluronan and a number of side chains of aggrecan bound to hyaluronan non-covalently. The loss of aggrecan from articular cartilage is considered to be a major factor in the development of osteoarthritis. Though enzymatic digestion of aggrecan is believed to be responsible for the release of aggrecan from osteoarthritic cartilage, other mechanisms, such as direct force-mediated detachment of aggrecan from hyaluronan may also be involved. In this study, the rupture force of the single bond between hyaluronan and aggrecan in articular cartilage was directly quantified using experimental measurement and Monte Carlo simulation. Low rupture force of this bond, as determined in this study suggested a possible direct force-mediated detachment of aggrecan from proteoglycan aggregate in osteoarthritic cartilage.

Aggrecans↗