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Effects of nonlinear strain-dependent permeability and rate of compression on the stress behavior of articular cartilage.

The compressive viscoelastic behavior of articular cartilage, a fiber-reinforced, porous, permeable solid matrix filled with water, is predominately governed by the flow of the interstitial water within the tissue and its exudation across the articular surface. The fluid flow is in turn governed by the permeability of the tissue and the loading imposed upon its surface. But for articular cartilage, the permeability depends nonlinearly on the strain; k = ko exp (Me). Here, M is the nonlinear flow-limiting parameter and e is the dilatation. In this investigation, we studied the influence of M and Ro = koHA/Uh (where HA is the elastic equilibrium modulus of the solid matrix, h is the tissue's thickness and U is the rate of compression applied onto the surface via a rigid, porous, free-draining filter) on the stress history of circular plugs of cartilage specimens attached to the bone. It was found that these two parameters have profound effects on the predicted compressive stress history. For very large Ro, the fluid flow effects become negligible. For small Ro and large M, large instantaneous compressive stresses several times larger than those observed at equilibrium are predicted. This amplification of compressive stress is due to the increase of importance of the relative fluid flow effect, i.e., Ro leads to 0, and nonlinear flow-limit effect, i.e., M greater than 0. Also, the theoretical curves predict that the rate of increase of stress initially decreases (convex) and finally becomes a constant. The results of our 5 percent offset compression experiments are in good agreement with the theoretical predictions.

Biomechanical Phenomena↗

Quantitative MR microscopy of enzymatically degraded articular cartilage.

Structural changes in bovine patellar articular cartilage, induced by component selective enzymatic treatments, were investigated by measuring tissue T(2) relaxation at 9.4 T. This MRI parameter was compared with Young's modulus, a measure of elastic stiffness and loadbearing ability of cartilage tissue. Collagenase was used to digest the collagen network and chondroitinase ABC to remove proteoglycans. Polarized light microscopy and digital densitometry were used to assess enzyme penetration after 44 hr of enzymatic digestion. T(2) relaxation in superficial cartilage increased significantly only in samples treated with collagenase. A statistically significant decrease in Young's modulus was observed in both enzymatically treated sample groups. These results confirm that T(2) of articular cartilage is sensitive to the integrity of collagen in the extracellular matrix. Nonetheless, it does not appear to be an unambiguous indicator of cartilage stiffness, which is significantly impaired in osteoarthrosis.

Animals↗

Articular Cartilage Chondrocytes are more Advantageous for Generating Hyaline-like Cartilage than Mesenchymal Cells Isolated from Microfracture Repairs.

Articular cartilage lacks self-repair capacity. Currently, two methods employing autologous cells are used to stimulate repair of articular cartilage. Micro-fracture induced repair induces autologous mesenchymal cell migration from bone marrow. Autologous chondrocytes' transplantation involves in vitro expansion of chondrocytes, and later implantation. In 15 patients de-differentiated chondrocytes obtained by cartilage biopsy were compared to cells derived from repair tissue induced by micro-fracture. These patients all underwent micro-fracture during the cartilage biopsy procedure. Autologous chondrocytes' transplantation was performed at least two months later then the biopsy. Tissue bits from articular cartilage and micro-fracture repair tissue were incubated in-vitro and explant cell cultures established. The cell cultures were assessed by immunohistochemistry and induced to differentiate. Differentiation into bone tissue was stimulated by addition of basic fibroblast growth factor, ascorbate and dexamethasone. High density (micro-mass) culture was used to stimulate chondrogenesis. Both cell cultures consist of mesenchymal progenitors as indicated by fibroblast growth factor receptor 3 expression and anti-CD-34+ antibodies. However, the micro-fracture generated repair tissue consists of osteocalcin-expressing cells destined to become bone. Collagen type II expression does not occur in these cells compared to autologous chondrocytes. Inducible nitric oxide synthase expression by microfracture cells is likely to damage surrounding articular cartilage in vivo. In conclusion, cells recruited by micro-fracture are inferior for cartilage regeneration purposes to those from cartilage biopsies.

Journal Article↗

Arthrographic study of the rheumatoid knee. Part 2. Articular cartilage and menisci.

The changes of the articular cartilage and of the menisci in 129 knee joints with classical rheumatoid arthritis have been investigated by an improved arthrographic technique. The changes of the intra-articular components on the arthrograms coincided well with direct views at arthroscopy and surgery. The changes of the articular cartilage on the arthrograms were graded as normal, deposit and pooling, thinning, filling defect, destruction, and disappearance, and those of the menisci as normal, degeneration, tear, and disappearance. The results showed that: (1) The radiographs did not always reflect the changes of those intra-articular components in the early stages; especially in stage 2 they showed various conditions from intact to destruction. (2) The changes of the menisci were less advanced than those of the articular cartilage in the early stages. (3) The changes in those components progressed almost symmetrically in both compartments. It is necessary to appreciate not only the pathological condition of the bones of the knee joints but also that of the intra-articular components to devise more careful programmes of treatment for rheumatoid knees.

Adult↗

The effects of immobilization on the characteristics of articular cartilage: current concepts and future directions.

OBJECTIVE: The purpose of this paper is to review current data and concepts concerning the effect of immobilization on articular cartilage in animal models. We also evaluate the methods to measure articular cartilage changes in humans. METHODS: Studies looking at the effects of immobilization on morphological, biochemical, and biomechanical characteristics of articular cartilage are reviewed. RESULTS: Articular cartilage changes in immobilized animals include altered proteoglycan synthesis, as well as thinning and softening of the tissue. The overall thickness of articular cartilage in the knee decreases up to 9% after 11 weeks of immobilization and the deformation rate under test load increases up to 42%. Quantitative data about changes in human articular cartilage following immobilization are not available. This is mainly due to the lack of an accurate, reproducible, and non-invasive method to characterize articular cartilage. DISCUSSION: An understanding of the alterations in articular cartilage following short and long term immobilization in humans is essential for the optimization of rehabilitation programs. Refined imaging techniques combined with state-of-the-art visualization tools could allow the systematical monitoring of articular cartilage morphology changes in immobilized humans.

Animals↗

[Changes in proteoglycans in human articular cartilage in relation to age].

The authors investigated in articular cartilage the presence and amount of the free fragment of the protein nucleus of the proteoglycan monomer containing the area of the bond with hyaluronic acid (HABR) and the presence of the small dermatan sulfate proteoglycan in relation to age. The articular cartilage of older subjects contains a much higher ratio of the protein fragment with functional HABR, as compared with young adult tissue. The more ready extractability of this fragment suggests an impaired bond between the proteoglycan monomer and hyaluronic acid. The ratio of the small dermatan sulfate proteoglycan is significantly reduced in the articular cartilage of older subjects. In the articular cartilage of a very old person (87 years) this proteoglycan was not detected or its content is at the borderline of detection of the methods used.

Adult↗

Correlation between articular cartilage collagenase activity and osteoarthritis.

Articular cartilage collagenase activity was determined for 28 sections obtained from twelve femoral heads. For each one square centimeter area, a section was graded by a histologic-histochemical grading system for the severity of the arthritis. Collagenase activity was found primarily in those areas of moderately severe disease, but not in mild or end stage arthritis.

Aged↗

High resolution, short echo time sodium imaging of articular cartilage.

The sodium present in articular cartilage interacts with the negatively charged proteoglycan aggregates in the matrix of the cartilage. Sodium images of short echo time may be useful for detecting changes that occur in the proteoglycan content of the cartilage. Such changes are indicative of early osteoarthritic damage, for example. Using an asymmetric short echo technique, sodium images of high resolution and signal-to-noise ratio that demonstrate anatomic features of the cartilage are presented. These images were obtained with echo times as short as 1 msec, at an in-plane resolution of 39 microns by 117 microns and signal-to-noise ratios of up to 40:1.

Cartilage, Articular↗

Microinjury to the synovial membrane may cause disaggregation of proteoglycans in rabbit knee joint articular cartilage.

Proteoglycans (PGs) isolated from articular cartilage (AC) of mature rabbits subjected to two or more consecutive intraarticular (IA) injections of sterile saline 24 h apart showed an aggregation defect in the presence of excess hyaluronic acid (HA). Although the PG contents of experimental and control cartilages were indistinguishable, a higher proportion of PGs were extractable from the 3 X IA tissues, as assessed by uronic acid analysis. Proteoglycans from experimental and control cartilages when examined by Sepharose CL-2B chromatography showed two subunit populations, the smaller (KAV = 0.70) containing more ketatan sulphate than the larger (KAV = 0.31). Cultures of AC from IA joints released more 35SO4-labelled PGs into the media over 72 h than control tissues and consisted mainly of PG degradation products although 20% could aggregate in the presence of HA. Examination of PG aggregation 2 weeks after 2 X IA or 3 X IA injections showed that the defect initiated was still present; however, cartilage of immature rabbits was not affected by the 2 X IA procedure.

Animals↗

S-100 protein immunostaining identifies cells expressing a chondrocytic phenotype during articular cartilage repair.

The healing of articular surface defects has been studied with conventional histology, which relies on the staining of the extracellular matrix to identify the phenotype of the cells present. A chondrospecific cellular marker would be useful. S-100 protein has been found in all chondroid tissues studied, and we evaluated its usefulness in the study of articular cartilage repair. Full-thickness rabbit femoral condylar defects were made, and the specimens were studied at serial time intervals. S-100 protein staining positively showed chondroid cells in the 7- and 14-day specimens, which were not identifiable by conventional techniques. At 30 and 60 days, an S-100 positive band of cells separated a deep safranin-O positive hypertrophic layer from a fibrocellular surface layer. At 120 days, the presence of S-100 protein identified cells with chondrogenic potential, and the lack of S-100 protein in other cells embedded in conventionally stained matrix suggested that these cells were no longer of a chondroid phenotype. The presence of S-100 protein-identified chondroid cells early in the repair process when the cells had not begun to synthesize conventionally stainable matrix and the lack of S-100 protein in cells late in the repair positively identified a phenotypic change earlier than conventional histology.

Animals↗

Morphological patterns of articular cartilage fibrillation.

The morphology of articular cartilage fibrillation is usually studied in sections cut vertical to the surface. The present study instead concerns the appearances seen when the surface is viewed en face. The study has been made on indian ink preparations of unfixed, hydrated tissue mounted in physiological saline and examined by stereomicroscopy at times 10 while in situ on the bone, and by transmitted light microscopy of tangential surface slices at magnifications up to times 150. The results are consistent with an hypothesis that fibrillation represents mechanically induced focal wear of the tissue. Various sorts of "minimal fibrillation" and other types of surface markings are illustrated. The en face pattern of the cartilage lesions is to some extent influenced by anatomical site, and it is suggested that it is modified by the local biomechanical environment and local character of the cartilage. Some, but not all, of the various patterns show orientation in the sense either of being predominantly unidirectional or of having two major alignments one at right-angles to the other. The differing relationships of this orientation, when present, to the direction of joint movement and to the alignment of the superficial collagen and its tensile strength, are described and discussed.

Adolescent↗

In vitro construction of cells-containing implants for articular cartilage regeneration.

Regeneration of destroyed articular cartilage can be induced by transplantation of cartilage cells into the defects. The best results are obtained by the use of either fetal allogeneic cells or autogenic ones. Induction of chondrogenesis in residual mesenchymal cells is optimal for obtaining large amounts of autogenic chondrocytes. Further modification of the technique is needed to reconstruct large defects. The cells are grown on biodegradable scaffolds and are later implanted into joint defects.

Animals↗

Hyaluronate in articular cartilage: age-related changes.

Articular cartilage of fetal calves, calves, and steers together with normal and osteoarthrotic human cartilage was analyzed for hyaluronate. The hyaluronate content increased with maturation in healthy tissue, particularly in regions of maximum contact, but was low in diseased cartilage.

Aging↗

A bimodular theory for finite deformations: Comparison of orthotropic second-order and exponential stress constitutive equations for articular cartilage.

Cartilaginous tissues, such as articular cartilage and the annulus fibrosus, exhibit orthotropic behavior with highly asymmetric tensile-compressive responses. Due to this complex behavior, it is difficult to develop accurate stress constitutive equations that are valid for finite deformations. Therefore, we have developed a bimodular theory for finite deformations of elastic materials that allows the mechanical properties of the tissue to differ in tension and compression. In this paper, we derive an orthotropic stress constitutive equation that is second-order in terms of the Biot strain tensor as an alternative to traditional exponential type equations. Several reduced forms of the bimodular second-order equation, with six to nine parameters, and a bimodular exponential equation, with seven parameters, were fit to an experimental dataset that captures the highly asymmetric and orthotropic mechanical response of cartilage. The results suggest that the bimodular second-order models may be appealing for some applications with cartilaginous tissues.

Algorithms↗

Structural studies on proteoglycan catabolism in rabbit articular cartilage explant cultures.

Mature rabbit articular cartilage cultures have been used to study the catabolism of aggregating proteoglycan monomers in normal cartilage. During the first 4 days of culture, about 40% of monomers are degraded and lose the ability to bind to hyaluronate. The non-aggregating products (NAgg-PG) have been isolated and compared structurally and immunologically to aggregating monomers (Agg-PG) purified from fresh tissue. The results show that: (1) NAgg-PG are smaller, more heterogeneous in size and have a lower protein/glycosaminoglycan ratio than Agg-PG. (2) NAgg-PG and Agg-PG have a very similar chondroitin sulfate/keratan sulfate ratio. (3) NAgg-PG have 25-50% lower disulfide content than Agg-PG. (4) NAgg-PG have only about 20% of the reactivity of Agg-PG towards a monoclonal antibody (12-20/1-C-6) specific for the hyaluronate binding region of the core protein. These results provide further evidence that proteoglycan catabolism in cartilage explants involves proteolysis of core protein resulting in separation of the hyaluronate binding region from the glycosaminoglycan-rich regions.

Animals↗

A matrix protein of Mr 55,000 that accumulates in human articular cartilage with age.

Adult human articular cartilage contains a protein of Mr 55,000 which is deficient in newborn cartilage. In the adult the molecule represents one of the most abundant non-collagenous, non-proteoglycan molecules in 4 M guanidinium chloride extracts of the tissue. The molecular size of the protein on SDS-PAGE remains constant under reducing and non-reducing conditions, suggesting that it does not exist as a disulphide-bonded multimer, nor do intramolecular disulphide bonds greatly influence its conformation. The protein has the ability to interact with some immunoglobulin preparations making its detection possible by Western blotting with some non-specific antisera. Labeling with [3H]leucine in organ culture indicates that protein of this size is being made by the chondrocytes. However, during purification the newly synthesized molecules do not behave as the resident protein on ion-exchange chromatography, suggesting that the protein may accumulate with age rather than being a major synthetic product of the adult chondrocytes. Amino terminal protein sequence analysis indicates that the N-terminus of the protein is blocked. Sequences derived from peptides generated with cyanogen bromide do not show homology with previously characterized proteins. Molecules of a similar size and composition have been described in bovine cartilage.

Adult↗

"Matrigenin" activity from bovine bone--II. Effects on the glycosaminoglycans of bovine articular cartilage in culture.

1. Bovine articular cartilage slices were studied in long term culture by periodically pulse-labelling the cultures with radiolabelled precursors of glycosaminoglycans and isolating the glycosaminoglycans from cartilage. 2. Pretreatment of the cartilage slices with bacterial collagenase resulted in stimulation of the incorporation of radioactivity into the glycosaminoglycans. 3. The addition of a fraction from bovine bone, enriched in "matrigenin" activity, to cultures of cartilage pretreated with collagenase resulted in an additional increase in the stimulation of incorporation of radioactivity.

Animals↗

The structure and synthesis of proteoglycans of articular cartilage.

The major proteoglycan of articular cartilage is a protein-polysaccharide of great complexity. The structure of this macromolecule is described in this article and is correlated to the function of proteoglycans within the extracellular matrix of cartilage. Chondrocytes, which comprise the cell population of cartilage, are responsible for the synthesis of proteoglycans. A description of the synthesis of proteoglycans reflects the complex nature of these macromolecules and involves a number of sites within various organelles of the chondrocyte. The pathway of proteoglycan synthesis is discussed in addition to the intracellular and extracellular events involved in the regulation of their biosynthesis.

Biological Transport↗