Human Knee Joint Cartilage Research Articles

Triple contrast computed tomography reveals site-specific biomechanical differences in the human knee joint-A proof of concept study.

Cartilage and synovial fluid are challenging to observe separately in native computed tomography (CT). We report the use of triple contrast agent (bismuth nanoparticles [BiNPs], CA4+, and gadoteridol) to image and segment cartilage in cadaveric knee joints with a clinical CT scanner. We hypothesize that BiNPs will remain in synovial fluid while the CA4+ and gadoteridol will diffuse into cartilage, allowing (1) segmentation of cartilage, and (2) evaluation of cartilage biomechanical properties based on contrast agent concentrations. To investigate these hypotheses, triple contrast agent was injected into both knee joints of a cadaver (N = 1), imaged with a clinical CT at multiple timepoints during the contrast agent diffusion. Knee joints were extracted, imaged with micro-CT (µCT), and biomechanical properties of the cartilage surface were determined by stress-relaxation mapping. Cartilage was segmented and contrast agent concentrations (CA4+ and gadoteridol) were compared with the biomechanical properties at multiple locations (n = 185). Spearman's correlation between cartilage thickness from clinical CT and reference µCT images verifies successful and reliable segmentation. CA4+ concentration is significantly higher in femoral than in tibial cartilage at 60 min and further timepoints, which corresponds to the higher Young's modulus observed in femoral cartilage. In this pilot study, we show that (1) large BiNPs do not diffuse into cartilage, facilitating straightforward segmentation of human knee joint cartilage in a clinical setting, and (2) CA4+ concentration in cartilage reflects the biomechanical differences between femoral and tibial cartilage. Thus, the triple contrast agent CT shows potential in cartilage morphology and condition estimation in clinical CT.

Predicting transport of intra-articularly injected growth factor fusion proteins into human knee joint cartilage

There are no drugs or treatment methods known to prevent the development of post-traumatic osteoarthritis (PTOA), a type of osteoarthritis (OA) that is triggered by traumatic joint injuries and accounts for ∼12% of the nearly 600 million OA cases worldwide. Lack of effective drug delivery techniques remains a major challenge in developing clinically effective treatments, but cationic delivery carriers can help overcome this challenge. Scaling up treatments that are effective in in vitro models to achieve success in preclinical in vivo models and clinical trials is also a challenging problem in the field. Here we use a cationic green fluorescent protein (GFP) as a carrier to deliver Insulin-Like Growth Factor 1 (IGF-1), a drug considered as a potential therapeutic for PTOA. GFP-IGF-1 conjugates were first synthesized as fusion proteins with different polypeptide linkers, and their transport properties were characterized in human cartilage explants. In vitro experimental data were used to develop a predictive mathematical transport model that was validated using an independent in vitro experimental data set. The model was used to predict the transport of these fusion proteins upon intra-articular injection into human knee joints. The predictions included results for the rate and extent of fusion protein penetration into cartilage, and the maximum levels of fusion proteins that would escape into systemic circulation through the joint capsule. Together, our transport measurements and model set the stage for translation of such explant culture studies to in vivo preclinical studies and potentially clinical application. Statement of significanceThe lack of blood supply in cartilage and rapid clearance of drugs injected into human knees presents a major challenge in developing clinically effective treatments for osteoarthritis. Cationic delivery carriers can target negatively charged cartilage and help overcome this problem. Scaling up treatments that are effective in vitro to achieve success in vivo is also challenging. Here, we use a cationic green fluorescent protein (GFP) to deliver Insulin-Like Growth Factor-1 (IGF-1) into cartilage. Experiments measuring transport of GFP-IGF-1 fusion proteins in human cartilage explants were used to develop and validate a mathematical model to predict fusion protein transport upon injection into human knee joints. This work translates such explant culture studies to in vivo preclinical studies and potentially clinical application.

Varying development of femoral and tibial subchondral bone tissue and their interaction with articular cartilage during progressing osteoarthritis.

Differences between tibial and femoral joint surfaces and knee compartments concerning coupled bone and cartilage turnover or bone-cartilage cross talk have not been previously examined, although the mechanical and biological interaction of the mineralized subchondral tissues with articular cartilage is of great importance for advancing osteoarthritis. Therefore, with the help of immunohistochemistry and real-time polymerase chain reaction (RT-PCR), human knee joint cartilage tissue was investigated for expression of key molecules of the extracellular matrix and cartilage composition (collagen type I and II, aggrecan) plus proteoglycan content (colorimetric analysis). Furthermore, we correlated the results with 3D microcomputed tomography of the underlying subchondral bone (high-resolution micro-CT system). Measurements were performed in dependence of the anatomical site (femoral vs. tibial, medial and lateral each) to identify regional differences during the osteoarthritic process. From an enduring series of 108 patients undergoing implantation of TKA, 34 osteochondral samples with lesions macroscopically classified as ICRS grade 1b (group A) and 34 samples with ICRS grade 3a/3b lesions (group B) were compared with 21 healthy controls. Concerning 3D analysis, the medial femoral condyle and tibia showed the most significant increase in bone volume fraction and a decrease in the trabecular number in group B frequently accompanied by subchondral bone resorption pits and enchondral ossification. Under physiological conditions, tibia plateaus show lower bone volume fraction than the corresponding femoral site and this difference enlarges with advancing OA. Partially even contradictory behavior was observed such as trabecular separation at the lateral tibial and medial plateau in osteochondral OA samples of the same patients. Collagen type II expression levels show faster and varying changes than type I during the OA process, leading to a lower positive or negative correlation with bone microstructural analysis, especially on the tibia plateau. Structural bone and cartilage parameter changes showed varying developments and correlations among each other in the different compartments of the knee. As a clinical conclusion, therapies to postpone or prevent cartilage degeneration by influencing the loss of mineralized bone could be site dependent.

Functional role of hedgehog pathway in osteoarthritis.

The hedgehog signalling pathway is one of the key regulators of metazoan development, and it plays an important role in the regulation of a variety of developmental and physiological processes. But it is aberrantly activated in many human diseases, including osteoarthritis (OA). In this study, we have reviewed the association of hedgehog signalling pathway in the development and progression of OA and evaluated the efforts to target this pathway for the prevention of OA. Usually in OA, activation of hedgehog induces up-regulation of the expression of hypertrophic markers, including type X collagen, increases production of nitric oxide and prostaglandin E2, several matrix-degrading enzymes including matrix metalloproteinase and a disintegrin and metalloproteinase with thrombospondin motifs in human knee joint cartilage leading to cartilage degeneration, and thus contributes in OA. Targeting hedgehog signalling might be a viable strategy to prevent or treat OA. Chemical inhibitors of hedgehog signalling is promising, but they cause severe side effects. Knockdown of HH gene is not an option for OA treatment in humans because it is not possible to delete HH in larger animals. Efficient knockdown of HH achieved by local delivery of small interfering RNA in future studies utilizing large animal OA models might be a more efficient approach for the prevention of OA. However, it remains a major problem to develop one single scaffold due to the different physiological functions of cartilage and subchondral bones possess. More studies are necessary to identify selective inhibitors for efficiently targeting the hedgehog pathway in clinical conditions.

Extracellular Distribution of Collagen II and Perifibrillar Adapter Proteins in Healthy and Osteoarthritic Human Knee Joint Cartilage.

Perifibrillar adapter proteins, interconnecting collagen fibrils, and linking the collagen network with the aggrecan matrix seem to play a crucial role in the pathogenesis of osteoarthritis (OA). Therefore, we examined immunohistochemically the extracellular distribution of collagen II and the main perifibrillar adapter proteins-collagen IX, decorin, cartilage oligomeric matrix protein (COMP), and matrilin-3-in human samples of healthy (n=4) and OA (n=42) knee joint cartilage. Histopathology assessment was performed using an OA score. Staining patterns were evaluated in relation to the disease stage. The perifibrillar adapter proteins were uniformly distributed in the upper zones of healthy cartilage. In moderate OA (n=8; score 14.3 ± 4.7), all proteins analyzed were locally absent in the fibrillated area or the superficial and upper mid zone. In advanced OA (n=20; score 18.9 ± 5.3), they were uniformly distributed in these zones and accumulated pericellularly. Perifibrillar adapter proteins are important for the stabilization of the collagen network in the upper zones of healthy cartilage. Their degradation might be a critical event in early OA. In advanced OA, there are indications for an increased synthesis in an attempt to regenerate the lost tissue and to protect the remaining cartilage from further destruction.

Three dimensional patient-specific collagen architecture modulates cartilage responses in the knee joint during gait

Site-specific variation of collagen fibril orientations can affect cartilage stresses in knee joints. However, this has not been confirmed by 3-D analyses. Therefore, we present a novel method for evaluation of the effect of patient-specific collagen architecture on time-dependent mechanical responses of knee joint cartilage during gait. 3-D finite element (FE) models of a human knee joint were created with the collagen architectures obtained from T2 mapped MRI (patient-specific model) and from literature (literature model). The effect of accuracy of the implementation of collagen fibril architecture into the model was examined by using a submodel with denser FE mesh. Compared to the literature model, fibril strains and maximum principal stresses were reduced especially in the superficial/middle regions of medial tibial cartilage in the patient-specific model after the loading response of gait (up to −413 and −26%, respectively). Compared to the more coarsely meshed joint model, the patient-specific submodel demonstrated similar strain and stress distributions but increased values particularly in the superficial cartilage regions (especially stresses increased >60%). The results demonstrate that implementation of subject-specific collagen architecture of cartilage in 3-D modulates location- and time-dependent mechanical responses of human knee joint cartilage. Submodeling with more accurate implementation of collagen fibril architecture alters cartilage stresses particularly in the superficial/middle tissue.

Importance of material properties and porosity of bone on mechanical response of articular cartilage in human knee joint--a two-dimensional finite element study.

Mechanical behavior of bone is determined by the structure and intrinsic, local material properties of the tissue. However, previously presented knee joint models for evaluation of stresses and strains in joints generally consider bones as rigid bodies or linearly elastic solid materials. The aim of this study was to estimate how different structural and mechanical properties of bone affect the mechanical response of articular cartilage within a knee joint. Based on a cadaver knee joint, a two-dimensional (2D) finite element (FE) model of a knee joint including bone, cartilage, and meniscus geometries was constructed. Six different computational models with varying properties for cortical, trabecular, and subchondral bone were created, while the biphasic fibril-reinforced properties of cartilage and menisci were kept unaltered. The simplest model included rigid bones, while the most complex model included specific mechanical properties for different bone structures and anatomically accurate trabecular structure. Models with different porosities of trabecular bone were also constructed. All models were exposed to axial loading of 1.9 times body weight within 0.2 s (mimicking typical maximum knee joint forces during gait) while free varus-valgus rotation was allowed and all other rotations and translations were fixed. As compared to results obtained with the rigid bone model, stresses, strains, and pore pressures observed in cartilage decreased depending on the implemented properties of trabecular bone. Greatest changes in these parameters (up to -51% in maximum principal stresses) were observed when the lowest modulus for trabecular bone (measured at the structural level) was used. By increasing the trabecular bone porosity, stresses and strains were reduced substantially in the lateral tibial cartilage, while they remained relatively constant in the medial tibial plateau. The present results highlight the importance of long bones, in particular, their mechanical properties and porosity, in altering and redistributing forces transmitted through the knee joint.

Lipid distribution in human knee and hip articular cartilage correlated to tissue surface roughness and surface active phospholipid layer presence: evidence of cooperative interfacial lipid delivery mechanisms

Lipid distribution in human knee and hip articular cartilage correlated to tissue surface roughness and surface active phospholipid layer presence: evidence of cooperative interfacial lipid delivery mechanisms

How do visual, spectroscopic and biomechanical changes of cartilage correlate in osteoarthritic knee joints?

Background Characteristic changes in cartilage of human knee joints with different degrees of osteoarthritis (OA) have been investigated by visual, biophotonical and biomechanical examination. Knowledge about the cartilage composition and changes during the development of OA is important for diagnostic decisions and understanding the pathogenesis of OA. Methods Thirty two patients with severe knee OA received endoprosthetic replacement. During surgical intervention cartilage specimen were harvested from defined surface areas of the joints. The degree of cartilage defects was classified visually (ICRS Grade: International Cartilage Repair Society), biophotonically (NIRS: near infrared spectroscopy) and biomechanically (Young’s Modulus). To characterise links between the investigated parameters the Spearman’s rank correlation coefficient was used. Findings Significant negative correlations were found between visual macroscopic degree of degeneration (ICRS Grade) and biophotonic characteristics (NIRS) ( ρ = −0.467) or cartilage stiffness (Young’s Modulus) ( ρ = −0.501). Between NIRS and Young’s Modulus significant positive correlation of ρ = 0.535 was detected. Interpretation Visual, biophotonic and biomechanical properties of cartilage reveal strong correlations in all degrees of cartilage defects in patients with severe OA. According to these results, we indicate that an objective, non-invasive and non-destructive measurement of cartilage properties during open and arthroscopic knee surgery is possible by NIRS and provide a novel tool to evaluate disease intervention and treatment.

Computational biomechanics of articular cartilage of human knee joint: Effect of osteochondral defects

Articular cartilage and its supporting bone functional conditions are tightly coupled as injuries of either adversely affects joint mechanical environment. The objective of this study was set to quantitatively investigate the extent of alterations in the mechanical environment of cartilage and knee joint in presence of commonly observed osteochondral defects. An existing validated finite element model of a knee joint was used to construct a refined model of the tibial lateral compartment including proximal tibial bony structures. The response was computed under compression forces up to 2000 N while simulating localized bone damage, cartilage–bone horizontal split, bone overgrowth and absence of deep vertical collagen fibrils. Localized tibial bone damage increased overall joint compliance and substantially altered pattern and magnitude of contact pressures and cartilage strains in both tibia and femur. These alterations were further exacerbated when bone damage was combined with base cartilage split and absence of deep vertical collagen fibrils. Local bone boss markedly changed contact pressures and strain patterns in neighbouring cartilage. Bone bruise/fracture and overgrowth adversely perturbed the homeostatic balance in the mechanical environment of articulate cartilage surrounding and opposing the lesion as well as the joint compliance. As such, they potentially contribute to the initiation and development of post-traumatic osteoarthritis.

CD47 associates with alpha 5 integrin and regulates responses of human articular chondrocytes to mechanical stimulation in an in vitromodel

BackgroundRecent studies provide evidence of roles for integrins in mechanical signalling in bone and cartilage. Integrin signalling is modulated by various mechanisms, including interaction with other transmembrane proteins. We aimed to identify whether one such protein, integrin-associated protein (CD47/IAP), is expressed by chondrocytes and whether it may regulate integrin-dependent mechanotransduction.MethodsChondrocytes, isolated from macroscopically normal and osteoarthritic articular cartilage of human knee joints, were studied in a resting state or following mechanical stimulation at 0.33 Hz. CD47/IAP expression and associations were confirmed by immunohistology, reverse transcription-polymerase chain reaction, Western blotting, and immunoprecipitation. Roles in mechanotransduction were studied by assessing effects of function-blocking antibodies on a range of electrophysiological, cellular, and molecular responses of primary chondrocytes and responses of CD47/IAP-null cell lines transfected with CD47/IAP.ResultsHuman articular chondrocytes were shown to express CD47/IAP, predominantly the type 2 isoform. Immunoprecipitation showed association of CD47/IAP with α5 integrin and thrombospondin but not SIRPα (signal-regulatory protein-alpha). The function-blocking anti-CD47/IAP antibody Bric 126 inhibited changes in membrane potential, tyrosine phosphorylation, and elevation of relative levels of aggrecan mRNA induced by mechanical stimulation, whereas in the presence of B6H12, an antibody that has partial agonist activity, a membrane depolarisation rather than a membrane hyperpolarisation response was induced by mechanical stimulation. CD47-null cell lines did not show changes in cell membrane potential following mechanical stimulation. Changes in cell membrane potential following mechanical stimulation were seen when CD47-null cells were transfected with CD47/IAP expression vectors but were not seen following mechanical stimulation of cells transfected with vectors for the extracellular immunoglobulin variable (IgV) domain of CD47/IAP in the absence of the transmembrane and intracellular domains.ConclusionCD47/IAP is necessary for chondrocyte mechanotransduction. Through interactions with α5β1 integrin and thrombospondin, CD47/IAP may modulate chondrocyte responses to mechanical signals.

Further work on the cryopreservation of articular cartilage with particular reference to the liquidus tracking (LT) method

The cryopreservation of articular cartilage with survival of living cells has been a difficult problem. We have provided evidence that this is due to the formation of ice crystals in the chondrons. We have developed a method in which the concentration of the cryoprotectant dimethyl sulphoxide (Me 2SO) is increased progressively, in steps, as cooling proceeds so that ice is never allowed to form, but the very high concentrations of Me 2SO required at low temperatures are reached only at those low temperatures. In this paper, we describe some new experiments with discs of ovine articular cartilage similar to those used in our previous studies and we show that continuous stirring throughout the process resulted in a significant increase in the rate of 35S sulphate incorporation into glycosoaminoglycans (GAGs), now reaching 87% of the corresponding fresh control values. We confirmed that the method is also effective for human knee joint cartilage, which gave 70% of fresh control ability to synthesise GAGs; continuous stirring was also used in this experiment. We then extended the method to ovine knee joint osteochondral dowels and showed that, again with continuous stirring, the method produced tissue concentrations of Me 2SO that were sufficient to prevent freezing in dowels too, and to permit cell function at 60% of control. The most important mechanical property (instantaneous compressive modulus) was unaffected by the process. Finally, we experimented with some technical variations to facilitate clinical use—a more rapid process for warming and removal of Me 2SO was developed and a method of short-term storage before or after cryopreservation was developed. Finally, pilot experiments were carried out to provide proof of principle for a closed, continuous flow method in which both temperature and Me 2SO concentration were computer-controlled.

Cyclodextrin polysulphates repress IL-1 and promote the accumulation of chondrocyte extracellular matrix

To evaluate the influence of cyclodextrin polysulphate (CDPS) on the extracellular matrix (ECM) metabolism of human articular cartilage chondrocytes. Isolated chondrocytes from femoral condyle cartilage of human knee joints were cultured in gelled alginate to maintain their differentiated phenotype. During 1 week of culture, the cells were exposed to different concentrations of CDPS. Synthesis of aggrecans was investigated in these cultures after using Na(2)(35)SO(4) as a radioactive precursor during the last 24h of culture. The artificial matrix was then solubilised with Na-citrate and newly synthesised aggrecan aggregates, accumulated during culture, were liberated and assayed. The isolated chondrocytes were labelled with antibodies against aggrecan and type II collagen to analyse the ECM molecules in the cell-associated matrix (CAM). Plasma membrane levels of receptors for insulin-like growth factor-1 (IGF-1RI) and for interleukin-1 (IL-1RI and IL-1RII), as well as levels of IGF-1, IL-1alpha and -beta were determined after the cells had been permeabilized and stained with the appropriate antibodies. The release of IL-6 in the culture media was used as a variable reflecting auto/paracrine IL-1 activity of the cells in different experimental conditions. CDPS significantly increased total (35)S-incorporation rates in ECM aggrecan. When compared with controls, CDPS-treated chondrocytes expressed significantly higher CAM aggrecan and type II collagen levels. As plasma membrane-bound IGFR1 and intracellular IGF-1 levels remained unchanged, this increase in accumulated CAM compounds may have resulted from suppressed catabolic activities by the chondrocytes in culture. CDPS-treated cells expressed significantly lower amounts of intracellular IL-1alpha and -beta levels. Plasma membrane-bound IL-1RI and decoy IL-1RII remained unchanged. beta-cyclodextrin-treated chondrocytes released significantly less IL-6 in the supernatant culture media. CDPS is a novel polysulfated polysaccharide showing cartilage structure modifying effects in vitro as it improves the synthesis of aggrecan and the accumulation of CAM macromolecules. This effect probably resulted in part from the downregulation of IL-1.

Expression profiles of two types of human knee-joint cartilage.

We have performed a comprehensive analysis of gene-expression profiles in human articular cartilage (hyaline cartilage) and meniscus (fibrocartilage) by means of a cDNA microarray consisting of 23,040 human genes. Comparing the profiles of the two types of cartilage with those of 29 other normal human tissues identified 24 genes that were specifically expressed in both cartilaginous tissues; these genes might be involved in maintaining phenotypes common to cartilage. We also compared the cartilage profiles with gene expression in human mesenchymal stem cells (hMSC), and detected 22 genes that were differentially expressed in cells representing the two cartilaginous lineages, 11 specific to each type, which could serve as markers for predicting the direction of chondrocyte differentiation. Our data should also provide useful information about regeneration of cartilage, especially in support of efforts to identify cartilage-specific molecules as potential agents for therapeutic approaches to joint repair.

Gene expression in chondrocytes assessed with use of microarrays.

Despite considerable limitations such as low sensitivity and insensitivity to alternative splicing, posttranscriptional regulation, and posttranslational modification, cDNA array technology provides a powerful tool with which to obtain an overview of gene expression patterns, hardly achievable with other techniques. This has been shown to be true for the analysis of known genes as well as the discovery of new genes of interest. Samples of normal and late-stage osteoarthritic cartilage of human knee joints were analyzed with use of the Human Cancer 1.2 cDNA-array and TaqMan analysis. In spite of a large variability of expression levels among different patients, significant expression patterns for many known genes of interest such as cartilage matrix proteins (e.g., collagen types II, VI, and XI; aggrecan; decorin; biglycan) and matrix-degrading proteases were detected. Of the latter, MMP-3 appeared to be strongly expressed in normal and early degenerative cartilage and downregulated in the late disease stages. This indicates that, in the late stages of cartilage degeneration, other degradation pathways might be more important, for example, those involving enzymes such as MMP-2 and MMP-13, both of which were upregulated in late-stage disease. Most results have to be considered to be preliminary to a certain degree, as technical tools and interpretation approaches are still emerging and need more validation. Clearly, there is a major challenge to distill information and knowledge out of the obtained mass of data. However, these data will be one basis of a new world of biological understanding. These new insights will be network-based and no longer molecule-centered. Today, molecules have a biochemical and physiological context; tomorrow, biological networks will have molecules as constituents.

Monoclonal Antibody 11-Fibrau: A Useful Marker to Characterize Chondrocyte Differentiation Stage

The aim of this study was to determine the feasibility of discriminating between differentiated and dedifferentiated chondrocytes by using the Mab 11-fibrau. Mab 11-fibrau did not bind to differentiated chondrocytes in cartilage of human knee joint, auricle, or nasal septum. During monolayer culture, when cells dedifferentiate, the number of 11-fibrau positive cells gradually increased and reached up to 100% after 4 passages. When differentiated chondrocytes were cultured in alginate, most (90–95%) of the cells remained 11-fibrau negative, in accordance with previous studies demonstrating that differentiated chondrocytes cultured in alginate keep their phenotype. Dedifferentiated (11-fibrau positive) cells were subjected to different redifferentiation regimes. As a well-known fact, cultures in alginate in medium where FCS was replaced by IGF1 and TGFβ2 results in increased collagen type II formation, indicative for redifferentiation. However, the cells remained 11-fibrau positive, suggesting they are not (yet) fully redifferentiated. On the other hand, when dedifferentiated cells (after 4 passages in monolayer culture) were seeded in a biomaterial and implanted subcutaneously in a nude mouse, the newly formed cartilage matrix contained collagen type II and the 11-fibrau staining on the cells had disappeared. Our results indicate that 11-fibrau may be a reliable and sensitive marker of chondrocyte phenotype.

Characterization of caveolins from human knee joint cartilage: expression of caveolin-1, -2, and -3 in chondrocytes and association with integrin β 1

Interactions between the extracellular matrix (ECM) and chondrocytes are of great importance for structure and function of cartilage. The present study was undertaken to answer the question whether caveolins take part in integrin-mediated cell-ECM interactions in the human cartilage. In samples of human knee joint cartilage, we detected the caveolin subtypes -1, -2, and -3 by immunohistochemical methods. Double-label experiments revealed a colocalization of caveolin with beta1-integrin. Results of immunoprecipitation and immunoblotting assays show that beta1-integrins associate with all three caveolin subtypes in human chondrocytes and indicate that they are part of the same complexes. Furthermore, immunoelectron microscopy shows the localization of beta1-integrin in caveolae-like structures of the cell membrane. The data stimulate further investigations on the role of the caveolin-integrin complex for integrin-mediated signaling pathways in chondrocytes.

A non-invasive technique for 3-dimensional assessment of articular cartilage thickness based on MRI part 1: Development of a computational method

Articular cartilage thickness is of relevance in various fields in diagnostics and biomedical research. In view of recent improvements of MR cartilage imaging a computational method has been developed for three-dimensional determination of cartilage thickness from tomographic datasets. A correction algorithm that compensates for the error implied in the voxel based distance measurements is implemented. Four different thickness definitions have been applied to two numerical test structures in order to judge their usability in the medical realm. The results for each of the thickness measurement methods are shown as color-coded thickness maps wrapped round the test objects. An algorithm determining at each point the minimal distance from the articular surface to the bone-cartilage interface is suggested to give the most suitable demonstration of articular cartilage. This algorithm is successfully applied to a 3-dimensional data set of human knee joint cartilage obtained with a fat-suppressed gradient-echo sequence from a healthy volunteer. A non-invasive method for determining cartilage thickness could become a very valuable tool in diagnostic radiology, orthopaedic practice and biomechanics.

Light and electron microscopical immunohistochemical localization of the small proteoglycan core proteins decorin and biglycan in human knee joint cartilage

Light and electron microscopical immunohistochemical localization of the small proteoglycan core proteins decorin and biglycan in human knee joint cartilage

Light and electron microscopical immunohistochemical localization of the small proteoglycan core proteins decorin and biglycan in human knee joint cartilage

The distribution of decorin and biglycan was investigated at the light and electron microscopical level in adult human articular cartilage. In general, the amount of decorin and biglycan was found to decrease with the depth of the layer of the cartilage. Decorin was found in the interterritorial matrix where most of the collagen is located. This fits in well with the assumption that decorin may modulate collagen metabolism. Biglycan was found next to the chondrocytes in the pericellular matrix and is assumed to be responsible for cellular activities. At the ultrastructural level, decorin was localized in the interterritorial matrix and in vesicles in chondrocytes. Biglycan was found, usually though not exclusively in the pericellular matrix. Both small proteoglycans were detected close to and on the collagen fibres and also associated with the more globular structures of the matrix between the fibrils. A double-staining approach revealed that the two molecules could be located along the same collagen fibril. However, staining for biglycan and decorin was not observed simultaneously within the same region of the fibre.