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Rehabilitation following surgical procedures to address articular cartilage lesions in the knee.

Knowledge of the structure and function of articular cartilage is important when considering rehabilitation following surgical procedures for articular cartilage lesions of the knee. Articular cartilage is avascular and derives its nutrition primarily from synovial fluid, resulting in a limited potential for regeneration. Basic science evidence has demonstrated that compressive loading may have a positive impact on articular cartilage healing; however, excessive shear loading may be detrimental. Rehabilitation following surgical procedures for articular cartilage lesions should include controlled range of motion exercises. Exercises to enhance muscle function must be done in a manner which minimizes shear loading of the joint surfaces in the area of the lesion. A period of protected weight bearing is often necessary and should be followed by progressive loading of the joint. This article will: 1) provide a brief review of the structure and function of articular cartilage lesions as it relates to rehabilitation; 2) describe common surgical procedures to address articular cartilage lesions; and 3) provide guidelines for rehabilitation following surgical management of articular cartilage lesions.

Animals↗

The possible role of neutrophil proteinases in damage to articular cartilage.

The proteolytic degradation of articular cartilage that is seen in the arthritides affects both of the major structural components of the tissue, proteoglycan and collagen. Neutrophil leucocytes are abundant in the synovial fluid of the inflamed joints, and we have considered whether the large quantities of neutral proteinases carried by these cells could contribute to the cartilage degradation. The two neutrophil serine proteinases have been isolated, and shown to break down both proteoglycan and collagen in articular cartilage. The enzymes attacked the non-helical terminal peptides of the collagen, eliminating the cross-links, thus destabilizing and solubilizing, the fibres. The soluble collagen then denatured spontaneously, and was further degraded. Although large quantities of the neutrophil proteinases are probably released in the synovial fluid each day, the inhibitory capacity of the fluid is seldom, if ever, saturated. Nevertheless, immunologically mediated release of the neutrophil enzymes in 'frustrated endocytosis' at the cartilage surface could give rise to the generalized damage that has been reported by others.

Animals↗

Meniscal and articular cartilage changes in knee osteoarthritis: a cross-sectional double-contrast macroradiographic study.

OBJECTIVE: In knee osteoarthritis (OA) damage to meniscal cartilage is associated with the changes in articular cartilage. Using double-contrast macroradiographs we determined whether the degree of meniscal cartilage damage was similar to or different from that at the corresponding regions of the articular cartilage on the tibia and femur. DESIGN: Double-contrast microfocal macroradiographs,x7-x9 magnification, were obtained of the tibio-femoral joint in 20 osteoarthritic knee patients with medial compartment disease (Kellgren and Lawrence grades I-III). The appearance of the meniscus and the femoral and tibial articular cartilage were graded separately using a 5-point scale. RESULTS: In the medial diseased compartment, articular cartilage damage on the tibia was similar to that of the meniscus, which had significantly greater (P<0.02) degenerative changes than the cartilage on the femur. In the lateral compartment, meniscal damage was significantly worse than in either tibial (P<0.04) or femoral articular cartilages (P<0.01), respectively; none was as severe as that in the medial osteoarthritic compartment. CONCLUSION: Although the cross-sectional nature of this study precluded definite aetiological inferences, this study showed that degenerative changes in the meniscal and articular cartilages were not totally variable. Because of its larger articular surface, changes in the medial femoral cartilage were less marked than at the meniscal and tibial cartilages in the osteoarthritic compartment. In the lateral compartment, meniscal damage precedes tibial and femoral articular cartilage changes. In knees with medial compartment OA, combined meniscal and articular cartilage damage would account for detection of radiographic joint space loss and not meniscal extrusion only.

Adult↗

Microfracture and bone morphogenetic protein 7 (BMP-7) synergistically stimulate articular cartilage repair.

OBJECTIVE: Microfracture is used to treat articular cartilage injuries, but leads to the formation of fibrocartilage rather than native hyaline articular cartilage. Since bone morphogenetic protein 7 (BMP-7) induces cartilage differentiation, we hypothesized that the addition of the morphogen would improve the repair tissue generated by microfracture. We determined the effects of these two treatments alone and in combination on the quality and quantity of repair tissue formed in a model of full-thickness articular cartilage injury in adolescent rabbits. DESIGN: Full-thickness defects were made in the articular cartilage of the patellar grooves of forty, 15-week-old rabbits. Eight animals were then assigned to (1) no further treatment (control), (2) microfracture, (3) BMP-7, (4) microfracture with BMP-7 in a collagen sponge (combination treatment), and (5) microfracture with a collagen sponge. Animals were sacrificed after 24 weeks at 39 weeks of age. The extent of healing was quantitated by determining the thickness and the surface area of the repair tissue. The quality of the repair tissue was determined by grading specimens using the International Cartilage Repair Society Visual Histological Assessment Scale. RESULTS: Compared to controls, BMP-7 alone increased the amount of repair tissue without affecting the quality of repair tissue. Microfracture improved both the quantity and surface smoothness of repair tissue. Compared to either single treatment, the combination of microfracture and BMP-7 increased both the quality and quantity of repair tissue. CONCLUSIONS: Microfracture and BMP-7 act synergistically to stimulate cartilage repair, leading to larger amounts of repair tissue that more closely resembles native hyaline articular cartilage.

Animals↗

A continuum theory and an experiment for the ion-induced swelling behavior of articular cartilage.

Swelling of normal bovine articular cartilage equilibrated in NaCl solutions was dimensionally measured in thin strips of tissue. The ion-induced strains show that free swelling of articular cartilage is anisotropic and inhomogeneous. For the molar concentrations used, contraction increased linearly with concentration, defining a "coefficient of chemical contraction" (alpha c). Isometrically constrained specimens registered a rise in tensile force followed by stress relaxation. An extension of the biphasic theory incorporating this ion-induced strain is proposed. This theory can describe the equilibrium anisotropic swelling behavior of cartilage and explain the transient force history observed in the isometric experiment.

Animals↗

Postnatal development of the collagen matrix in rabbit tibial plateau articular cartilage.

Changes in the 3-dimensional arrangement of the articular cartilage matrix during growth of the rabbit tibial plateau were studied. Knees from newborn, and 1, 2 and 6 wk-old rabbits were compared with those of adults by light and electron microscopy. The specimens were fixed, embedded en bloc in epoxy resin and sectioned vertically/coronally through the point where the articular cartilage was thickest in the adult medial tibial plateau. At birth, the proximal tibial epiphysis was cartilaginous, but nascent articular cartilage was recognisable as a densely cellular layer covering the tibial condyle. Within 30 microns of the articular surface, the chondrocytes were flattened and collagen fibres ran among these cells in a direction parallel to the surface. Deeper in the articular cartilage, rounded cells were evenly distributed within a random collagen fibril network. At the centre of the plateau, the tangential layer changed little during growth, whereas the subjacent cellular layer grew in thickness and steadily achieved a more vertical character in the organisation of its constituent collagen and cellular elements. At 1 wk, cells were separated into clusters by acellular regions filled with collagen fibrils. At 2 wk, cells within the forming radial zone were aligned in columns bracketed by vertical collagen fibres. Continuity of these vertical fibres with those in the tangential surface layer was evident at this age. The chondrocytes were surrounded by fibrous capsules typical of chondrons. By 6 wk, the bases of the radial collagen fibres in the very centre of the condyle had calcified, as had the adjacent hypertrophic hyaline cartilage. A solid subchondral plate and tidemark did not appear until skeletal maturity. From birth to age 6 wk, maximum thickness of the layer identified as primordial articular cartilage increased from 0.13 mm to 0.70 mm, and was 1.5 mm in the adult. Throughout growth, however, the thickness of the tangential layer in the centre of the plateau never exceeded 0.05 micron. In the patella, femoral head and peripheral tibial plateau, cartilage development followed the same general sequence. In contrast to the central tibial plateau, the tangential layer also grew in thickness, but at a slower rate than that of the radial zone. At all ages, the developing articular cartilage was structurally distinct from the deeper hyaline cartilage which contributed to growth of the ossification centre through enchondral ossification. The collagen matrix of articular cartilage acquires a characteristic, orderly 3-dimensional structure soon after birth. Growth in cartilage thickness occurs primarily through enlargement of the radial zone.

Animals↗

Solute diffusivity correlates with mechanical properties and matrix density of compressed articular cartilage.

The biomechanical functions of articular cartilage are governed largely by the composition and density of its specialized extracellular matrix. Relationships between matrix density and functional indices such as mechanical properties or interstitial solute diffusivities have been previously explored. However, direct correlations between mechanical properties and solute transport parameters have received less attention, despite potential application of this information for cartilage functional assessment both in vivo and in vitro. The objective of this study was therefore to examine relationships among solute diffusivities, mechanical properties, and matrix density of compressed articular cartilage. Matrix density varied due to natural variation among explants and due to applied static compression. Matrix density of statically compressed cartilage explants was characterized by glycoaminoglycan (GAG) weight fraction and fluid volume fraction, while diffusion coefficients of a wide range of solutes were measured to characterize the transport environment. Explant mechanical properties were characterized by a non-linear Young's modulus (axial stress-strain ratio) and a non-linear Poisson's ratio (radial-to-axial strain ratio). Solute diffusivities were consistently correlated with Young's modulus, as well as with explant GAG weight and fluid volume fractions. Therefore, in vitro mechanical tests may provide a means of assessing transport environments in cartilage-like materials, while in vivo measurements of solute transport (for example with magnetic resonance imaging) may be a useful complement in identifying localized differences in matrix density and mechanical properties.

Animals↗

Effects of moving training on histology and biomarkers levels of articular cartilage.

OBJECTIVE: To study the adaptation process and extent of articular cartilage in the canine knee joint to different modes of movements and to investigate if levels of cartilage oligomeric matrix protein (COMP), matrix metalloproteinases-1 (MMP-1), matrix metalloproteinases-3 (MMP-3), and tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) in serum and synovial fluid can be used to predict effectively early sports injury and remolding degree of articular cartilage in the canine knee. MATERIALS AND METHODS: Twenty adult dogs divided randomly into three groups (eight in the common training group, Training Group; eight in the intensified training group, Intensified Group; and four in the Control Group) were trained daily at different intensities. Magnetic resonance imaging (MRI) examinations were performed regularly (0, 2, 4, 6, 8, 10 weeks) to investigate changes of articular cartilage in the canine knee, while concentrations of COMP, MMP-1, MMP-3, and TIMP-1 in serum and synovial fluid were measured by ELISA assays. All of the dogs were euthanized after training for 10 weeks, and all of the knee joints were taken out to be examined histologically. RESULTS: We could find imaging changes of early sport injury of articular cartilage in the Training Group and Intensified Group by MRI examination after 2 weeks of training; the damage images were most severe in 4-6 weeks, and then lightened gradually. We could not find the difference of cartilage injury and repair degree in MRI images between these two groups at different time points. Elevations of levels of COMP, MMP-1, MMP-3, TIMP-1, and MMP-3/TIMP-1 in serum and synovial fluid were seen during the training period, and their levels changed remarkably at different times. Levels of MMP-1, MMP-3, and MMP-3/TIMP-1 in the Intensified Group were lower than that in the Training Group in general, and levels of COMP were higher, which hinted that the injury trend of articular cartilage in the Intensified Group was lower than that in the Training group, and the repair trend was higher. Furthermore, there were statistically significant associations between biomarker levels in serum and in synovial fluid. Histological examinations in 10 weeks demonstrated that the signs of cartilage damage and repair in canine knee joint in the Training Group and the Intensified Group were obvious, and the Intensified Group could do better than the Training Group in promoting remodeling reconstruction of articular cartilage. CONCLUSIONS: High-intensity and repetitive movement may easily induce sports injury, and it is followed with a repair process; intensified training can do better than common training in promoting remodeling reconstruction of articular cartilage. The sensitivity of these biomarkers reflecting articular cartilage pathological changes is better than MRI, and the associated application of several biomarkers to predict the extent of damage and repair, as well as changes of metabolism in articular cartilage, and to monitor change of disease course has very good value for clinical application.

Animals↗

Sequential changes in the mechanical properties of viable articular cartilage stored in vitro.

Viable articular cartilage from the medial femoral condyles of rabbits was stored in vitro in tissue culture medium with various additives and the same site of each specimen was mechanically tested sequentially throughout a 12-day storage period. Indentation testing was performed with instantaneous and sustained loads. Preservation of sustained-load carrying capacity was observed in the condyles stored with additives, indicating maintenance of an intact cartilage matrix. However, initial testing with small sustained loads (preload) showed changes not observed at higher load levels. The changes noted at small sustained initial loads may reflect alterations in cartilage surface structure and may be an early indicator of its mechanical integrity. Chondrocyte viability and proteoglycan content, as measured by 35S incorporation and hexosamine concentration, were unchanged in comparison to fresh articular cartilage.

Animals↗

Use of synovial fluid markers of cartilage synthesis and turnover to study effects of repeated intra-articular administration of methylprednisolone acetate on articular cartilage in vivo.

In vivo the effects of intra-articular (IA) corticosteroids on articular cartilage remain controversial. This study was designed to examine this issue using synovial fluid (SF) markers of cartilage metabolism. Paired radiocarpal joints, without clinical or radiographic signs of joint disease, were studied in 10 adult horses. Aseptic arthrocentesis was performed weekly for 13 weeks. IA injections of methylprednisolone acetate (MPA) into the treatment joint and the vehicle into the control joint were performed at weeks 3, 5 and 7. We used radioimmunoassays on SF samples which measure a keratan sulfate epitope (KS) and the 846 epitope on cartilage aggrecan (PG) and the C-propeptide (CPII) of cartilage type II procollagen which is released following synthesis of this molecule. Gel chromatography was performed on selected SF samples to evaluate the sizes of SF PG molecules. The total joint KS and the 846 epitopes were both present on a heterogeneous population of mainly molecules which, from chromotographic analysis, appeared to be mainly fragments of the articular cartilage aggrecan. They were significantly elevated in MPA joints whereas CPII was significantly reduced compared to the control during the treatment period. These results indicate that the repeated use of IA MPA leads to a potentially harmful inhibition of procollagen II synthesis and an increased release of degradation products of the PG aggrecan from articular cartilage.

Aggrecans↗

Novel articular cartilage structure in the South American opossum, Monodelphis domestica.

Articular cartilage provides smooth surfaces for low-friction, unrestricted movement of opposing skeletal elements. The surface topography of articular cartilage has been the subject of numerous studies and, with few exceptions, is considered to be smooth (at least at the light microscopic level). Some studies have reported 'humps' on the articular surface which have been related to underlying chondrocytes residing very close to the surface. Here we report on a highly nodular form of articular cartilage in the distal limb joints of the South American opossum, Monodelphis domestica. Unlike previous reports, these articular 'humps' are visible under a dissecting microscope. Each 'hump' or 'nodule' represents the surrounding matrix of single or sometimes paired rounded chondrocytes. Flattened chondrocytes normally associated with mammalian articular cartilage were absent from these joints. Interestingly, the articular cartilage of the more proximal limb joints such as the knee showed more typical features of articular cartilage including flattened superficial chondrocytes.

Animals↗

Histopathological and histoenzimological investigations of the rheumatoid articular cartilage.

Twenty seven biopsies of articular cartilage taken intraoperatively from patients with Rheumatoid arthritis (RA) and from control patients with traumas were examined using histopathological techniques (HE, VG, PAS-Alcian, Gömöri, Safranine 0) and histoenzymological techniques (Acid phosphatase-lysomal marker, Chondroitinsulphatase, Peroxidase). Histopathologically, the rheumatoid articular cartilage appears with superficial and deep cartilaginous fissures, frequent perichondrocytic gaps associated with modification of the tinctorial activity. At the pannus synovia-cartilage junction we found invasive and destructive synovial inflammatory infiltrates penetrating and eroding the cartilage. Histoenzymologically, the rheumatoid chondrocytes have a high lysosomal potential (phosphatasic, chondroitinsulphatasic) and highly oxidative potential (peroxidasic) specific for lesion modifications.

Acid Phosphatase↗

Radiography of rabbit articular cartilage with diffraction-enhanced imaging.

Articular cartilage of synovial joints is not visible with conventional X-ray imaging. Hence, the gradual degeneration and destruction of articular cartilage, which is characteristic of degenerative joint diseases, is only detected at a late stage when the cartilage is lost and the joint space that it once occupied narrows. The development of an X-ray imaging technique that could detect both the degenerative cartilage and bone features of joint diseases is of special interest. Here we show, for the first time, that a high-contrast imaging technique, diffraction-enhanced X-ray imaging (DEI), allows the visualization of articular cartilage of both disarticulated and articulated rabbit knee joints. Furthermore, a single cartilage lesion can be visualized within an intact joint. The results suggest that DEI has the potential to be of use in the study of cartilage degeneration.

Animals↗

Use of novel interactive input devices for segmentation of articular cartilage from magnetic resonance images.

OBJECTIVE: To study the effect of new interactive computer input devices on cartilage segmentation in terms of time, consistency between input devices, and precision in quantitative magnetic resonance imaging (qMRI). DESIGN: We compared two new input devices, an interactive digitizing tablet and an interactive touch-sensitive screen, to a traditional mouse. Medial tibial and patellar cartilage of six healthy and six osteoarthritic knees were segmented using each input device. Cartilage volume, surface area and mean thickness were assessed using a validated algorithm and used to determine consistency and precision. Segmentation time was also measured. RESULTS: Segmenting with an interactive touch-sensitive screen reduced segmentation time by 15% when compared to the traditional mouse but we found no significant difference in segmentation time between the interactive digitizing tablet and the traditional mouse. We found no difference in consistency or precision of cartilage volume, mean thickness or surface area between the three input devices tested. CONCLUSIONS: We conclude that measurements of cartilage made using articular cartilage segmentation from MR images are independent of the input device chosen for user interaction.

Adult↗

Inhibition of adenosine kinase attenuates interleukin-1- and lipopolysaccharide-induced alterations in articular cartilage metabolism.

OBJECTIVE: To investigate the effect of adenosine kinase inhibition on interleukin (IL)-1beta- and lipopolysaccharide (LPS)-induced cartilage damage. DESIGN: Articular cartilage was obtained from the metacarpophalangeal joints of 10 young adult horses. Following a stabilization period, weighed cartilage explants were exposed to IL-1beta (10 ng/ml) or LPS (50 microg/ml) to induce cartilage degradation. To test the potential protective effects of adenosine, these explants were simultaneously exposed to adenosine (100 microM), the adenosine kinase inhibitor 5'iodotubercidin (ITU, 1 microM) or to both adenosine and ITU. After 72 h in culture, conditioned medium was collected for evaluation of glycosaminoglycan (GAG), nitric oxide (NO), prostaglandin E2 (PGE2) and matrix metalloproteinase (MMP)-3 release. RESULTS: IL-1beta and LPS stimulated significant release of GAG, NO, PGE2 and MMP-3. Incubation with ITU significantly inhibited both IL-1beta- and LPS-induced GAG release, but did not alter MMP-3 production. Exposure to ITU also reduced IL-1beta-induced PGE2 release and LPS-induced NO production. Direct adenosine supplementation did not attenuate the effects of IL-1beta or LPS, and the addition of adenosine or ITU in the absence of IL-1beta or LPS did not have any detectable effect on cartilage metabolism in this model. CONCLUSIONS: The adenosine kinase inhibitor ITU attenuated experimentally induced cartilage damage in an in vitro cartilage explant model. Release of adenosine from chondrocytes may play a role in the cellular response to tissue damage in arthritic conditions and modulation of these pathways in the joint may have potential for treatment of arthropathies.

Adenosine↗

Transport and binding of insulin-like growth factor I through articular cartilage.

This study focused on the role of insulin-like growth factor (IGF) binding proteins (IGFBPs) in cartilage on the transport and binding of IGF-I within the tissue. We have developed experimental and theoretical modeling techniques to quantify and contrast the roles of diffusion, binding, fluid convection, and electrical migration on the transport of IGF-I within cartilage tissue. Bovine articular cartilage disks were equilibrated in buffer containing 125I-IGF-I and graded levels of unlabeled IGF-I. Equilibrium binding, as measured by the uptake ratio of 125I-IGF-I in the tissue (free plus bound) to the concentration of labeled species in the buffer, was found to be consistent with a first-order reversible binding model involving one dominant family of binding sites within the matrix. Western ligand blots revealed a major IGF binding doublet around 23 kDa, which has been previously shown to coincide with IGFBP-6. Diffusive transport of 125I-IGF-I through cartilage was measured and found to be consistent with a diffusion-limited reaction theoretical model incorporating first-order reversible binding. Addition of excess amounts of unlabeled IGF-I during steady state transport of 125I-IGF-I resulted in release of bound 125I-IGF-I from the tissue, as predicted by the diffusion-reaction model. In contrast, addition of the low-affinity Des(1-3)IGF-I analog did not result in release of bound 125I-IGF-I. Application of electric current was used to augment transport of IGF-I through cartilage via electroosmosis and electrophoresis. Taken together, our results suggest that a single dominant substrate family, the high-affinity IGFBPs, is responsible for much of the observed binding of IGF-I within cartilage. The data suggest that intratissue fluid flow, such as that induced by mechanical loading of cartilage in vivo may be expected to enhance IGF transport by an order of magnitude and that this increment may help to counterbalance the restrictions encountered by the immobilization of IGFs by the binding proteins.

Animals↗

The matrix components of the epiphyseal growth plate and articular cartilages from dogs treated with ammonium tetrathiomolybdate, a copper antagonist.

As part of a project to study the effect of copper deficiency (CD) on bone development in young dogs, the composition and metabolism of proteoglycans (PGs) and extractability of collagens in the epiphyseal growth plate cartilage (EGPC) and articular cartilages (AC) were investigated. Copper deficiency was induced by feeding ammonium tetrathiomolybdate (TTM) a copper antagonist. The collagen of cartilages from TTM-treated animals was significantly more soluble in 0.5 saline than control tissues. While no distinction between TTM-treated and control cartilages was evident in terms of PG content or extractability under associative (0.5 M-GuHCl) or dissociative (4.0 M-GuHCl) conditions, the sedimentation behaviour of the PG aggregates following CsCl density gradient ultracentrifugation suggested less polydispersity of PGs in preparations from the TTM-treated animals. Moreover, analysis of the PG monomers from EGPC of TTM animals showed galactosamine/glucosamine ratios higher than control preparations, suggesting a reduced keratan sulphate content in these preparations. Organ culture of EGPC showed a significant reduction in the incorporation of 35S into PGs and of 3H-thymidine into DNA in the tissues of TTM-treated animals relative to controls. From these findings we deduce that the catabolism of PGs and the extent of collagen cross-linking in EGPC of TTM-treated animals may be reduced relative to age-matched control tissues.

Animals↗