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Articular cartilage lesions and anterior knee pain.

The present case-control study included as cases 24 athletes with anterior knee pain, and 17 controls, matching the cases according to gender and age. All cases had their most symptomatic knee examined by magnetic resonance imaging (MRI). Among controls one knee was chosen for examination at random. The MRI of the patella showed articular cartilage lesions in 17 out of 24 cases, whereas among the controls 4 out of 17 had articular cartilage lesions. (Odds Ratio 7.9 (95% confidence interval 1.9-33)). However, presence of articular cartilage lesions was not associated with duration of symptoms or intensity of the anterior knee pain. The present study showed a significant positive association between presence of articular cartilage lesions in the patella and presence of anterior knee pain, but further studies are needed to examine the relationship in detail.

Adult↗

The role of viscoelasticity of collagen fibers in articular cartilage: axial tension versus compression.

The role of viscoelasticity of collagen fibers in bovine articular cartilage was examined in compression and tension using stress relaxation measurements in the axial direction (normal to the articular surface). Experimentally, for a given axial strain, both peak and equilibrium loads were higher in tension than in compression, whereas stress relaxation was stronger in compression, as indicated by the higher peak-to-equilibrium ratios. A viscoelastic fibril-reinforced model including fluid flow was used for analysis of the experimental data. The collagen fibrillar matrix was assumed to be viscoelastic with a strain-dependent tensile modulus, and the nonfibrillar matrix was modeled as linearly elastic. For axial tension, collagen viscoelasticity was found to account for most of the stress relaxation, while the effects of fluid pressurization on the tensile stress were negligible. In contrast, for axial compression, the dominant mechanism for stress relaxation arose from fluid pressurization, while the associated relaxation in collagen fibers mainly resulted in an increase in radial strain. The effective Poisson's ratio, defined as the ratio of the radial and axial strains, was generally smaller in compression than in tension, and deviated from the true Poisson's ratio in tensile tests because of the frictional contacts between the specimen and the loading platens. Furthermore, lower collagen elasticity in the axial direction was observed than in the radial direction. This study illustrates the essential role of collagen viscoelasticity and interstitial fluid pressurization in the mechanical response of articular cartilage.

Animals↗

Microspectrophotometric quantitation of glycosaminoglycans in articular cartilage sections stained with Safranin O.

A new microspectrophotometric method was developed for quantitation of glycosaminoglycans with Safranin O dye in articular cartilage matrix. From histological sections molar extinction coefficient of Safranin O was determined and used to measure the dye content of the sections. The amount of glycosaminoglycans was determined with depth of bovine articular cartilage by both gas chromatography and thin layer chromatography to calculate the fixed negative charge content. Comparison between the results revealed that binding of Safranin O to glycosaminoglycan polyanions was stoichiometric and showed minimal nonspecific staining. The method provides an accurate technique for quantitation and localization of fixed negative charge content of glycosaminoglycans in the articular cartilage matrix. Specific enzyme digestions enable detection of separate glycosaminoglycans.

Animals↗

Basic science of articular cartilage repair.

As the ability to understand the peculiarities of successful healing of articular cartilage defects moves forward, it becomes clear that this complex orthopaedic problem soon will be successfully addressed. A multidisciplinary approach, combining clinical experience, cogent biomaterial designs, new cell biologic processes, biomechanical assessment, and modern molecular biology, clearly is leading toward clinically acceptable, viable, and consistent articular cartilage regeneration.

Biomechanical Phenomena↗

Articular-cartilage matrix gamma-carboxyglutamic acid-containing protein. Characterization and immunolocalization.

Matrix gamma-carboxyglutamic acid (Gla)-containing protein (MGP) was found to be present in articular cartilage by Western-blot analysis of guanidinium chloride extracts of human and bovine cartilage and was further localized by immunohistochemical studies on human and monkey specimens. In newborn articular cartilage MGP was present diffusely throughout the matrix, whereas in growth-plate cartilage it was seen mainly in late hypertrophic and calcifying-zone chondrocytes. In adult articular cartilage MGP was present primarily in chondrocytes and the pericellular matrix. Immunoelectron microscopy studies revealed an association between MGP and vesicular structures with an appearance consistent with matrix vesicles. MGP may be an important regulator of cartilage calcification because of its localization in cartilage and the known affinity of Gla-containing proteins for Ca2+ and hydroxyapatite.

1-Carboxyglutamic Acid↗

Incompressibility of the solid matrix of articular cartilage under high hydrostatic pressures.

The objective of this study was to test the hypothesis that the organic solid matrix of articular cartilage is incompressible under physiological levels of pressure. Due to its anisotropic swelling behavior, an anisotropic version of the biphasic theory was used to predict the deformation and internal stress fields. This theory predicts that, under hydrostatic loading of cartilage via a pressurized external fluid, a state of uniform hydrostatic fluid pressure exists within the tissue regardless of the anisotropic nature of the solid matrix. The theory also predicts that if the solid matrix is intrinsically incompressible, the tissue will not deform under hydrostatic loading conditions. This prediction, i.e., no deformation, was experimentally tested by subjecting specimens of normal bovine articular cartilage to hydrostatic pressures. A new high pressure hydrostatic loading chamber was designed and built for this purpose. It was found that normal bovine articular cartilage, when subject to hydrostatic pressures up to 12 M Pa, does not deform measurably. This experimental finding supports one of the fundamental assumptions of the biphasic theory for cartilage, i.e., the organic solid matrix of the tissue is intrinsically incompressible when loaded within the normal physiologic range of pressures. Hydrostatic loading has often heen used in cartilage explant cultures for tissue metabolism studies. The findings of this study provides an accurate method to calculate the states of stress acting on the fluid and solid phases of the tissue in these hydrostatically loaded explant culture experiments, and suggest that tissue deformation will be minimal under pure hydrostatic pressurization.

Algorithms↗

Destruction of articular cartilage by arthritic synovium in vitro: mechanism of breakdown and effect of indomethacin and prednisolone.

Arthritic synovial tissue when cultured with normal articular cartilage induces a breakdown of articular cartilage proteoglycans. No collagen breakdown occurs unless the macroglobulins are inactivated by pretreatment with acid. Proteoglycan breakdown is most likely due to the continuous secretion of hydrolases by the synovium. A proteolytic enzyme has been found in the culture medium which has a pH optimum around 7.6, and is Ca++ dependent. Both indomethacin and hydrocortisone are inhibitors of proteoglycan breakdown.

Animals↗

Photodynamic treatment has chondroprotective effects on articular cartilage.

Osteoarthritis (OA) is a disabling joint disease for which there is currently no cure. It is characterized by the destruction of articular cartilage. One strategy that is being explored for protecting the cartilage in OA is the administration of transforming growth factor-beta, which in vitro antagonizes cartilage degradation initiated by catabolic stimulants such as interleukin-1 (IL-1). The problems associated with selective delivery of the growth factor to chondrocytes, undesirable side-effects on joint tissues, and short biological half-life have led us to explore modalities aimed at activating transforming growth factor-beta that is stored in the cartilage as latent complexes. Photodynamic therapy is a two-step protocol of tissue sensitization with a light-activatable chemical called a photosensitizer followed at some interval by irradiation with the appropriate wavelength visible light. Biological effects are typically elicited through oxygen-dependent photochemistry without heat generation. Transforming growth factor-beta1 can be activated by oxidative mechanism(s), prompting us to explore whether photodynamic technology can be harnessed to modulate cartilage metabolism. Disks of bovine articular cartilage were photosensitized by incubation with a chlorin(e6)-succinylated polylysine conjugate and irradiated with 1-2 J/cm2 red light (lambdamax = 671 nm). This two-step regimen dramatically inhibited IL-1-stimulated proteoglycan degradation and concomitantly increased latent and active transforming growth factor-beta1 in culture medium. This research may lead to the development of minimally invasive photodynamic therapy in which light is delivered to locally activate a chondroprotective program in photosensitized cartilage in the context of OA.

Animals↗

MR imaging of articular cartilage using driven equilibrium.

The high incidence of osteoarthritis and the recent advent of several new surgical and non-surgical treatment approaches have motivated the development of quantitative techniques to assess cartilage loss. Although magnetic resonance (MR) imaging is the most accurate non-invasive diagnostic modality for evaluating articular cartilage, improvements in spatial resolution, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) would be valuable. Cartilage presents an imaging challenge due to its short T(2) relaxation time and its low water content compared with surrounding materials. Current methods sacrifice cartilage signal brightness for contrast between cartilage and surrounding tissue such as bone, bone marrow, and joint fluid. A new technique for imaging articular cartilage uses driven equilibrium Fourier transform (DEFT), a method of enhancing signal strength without waiting for full T(1) recovery. Compared with other methods, DEFT imaging provides a good combination of bright cartilage and high contrast between cartilage and surrounding tissue. Both theoretical predictions and images show that DEFT is a valuable method for imaging articular cartilage when compared with spoiled gradient-recalled acquisition in the steady state (SPGR) or fast spin echo (FSE). The cartilage SNR for DEFT is as high as that of either FSE or SPGR, while the cartilage-synovial fluid CNR of DEFT is as much as four times greater than that of FSE or SPGR. Implemented as a three-dimensional sequence, DEFT can achieve coverage comparable to that of other sequences in a similar scan time. Magn Reson Med 42:695-703, 1999.

Cartilage, Articular↗

An analysis of the squeeze-film lubrication mechanism for articular cartilage.

An asymptotic analysis of a lubrication problem is presented for a model of articular cartilage and synovial fluid under the squeeze-film condition. This model is based upon the following constitutive assumptions: (1) articular cartilage is a linear porous-permeable biphasic material filled with a linearly viscous fluid (i.e. Newtonian fluid); (2) synovial fluid is also a linearly viscous fluid. The geometry of the problem is defined by assuming that (1) cartilage is a uniform layer of thickness H; (2) synovial fluid is a very thin layer compared to H; (3) the radius R of the load-supporting area (or the effective radius of curvature of joint surface, Ri) is large compared to H. Squeeze-film action is generated in the lubricant by a step loading function applied onto the two bearing surfaces. The model assumptions and the material properties yield two small parameters in the mathematical formulation. Based on these two small parameters, two coupled nonlinear partial differential equations were derived from an asymptotic analysis of the problem: one for the lubricant (analogous to the Reynolds equation) and one for the cartilage. For known properties of normal cartilage, our calculations show: (1) the cartilage layer deforms to enlarge the load-supporting area; (2) cartilage deformation acts to reduce the lateral fluid speed in the lubricant, thus prolonging the squeeze-film time which ranges from 1 to 10 s; (3) lubricant fluid in the gap is forced from the central high-pressure region into cartilage, and expelled from the tissue at the low-pressure periphery of the load-bearing region; and (4) tensile hoop stress exists at the cartilage surface despite the compressive squeeze-film loading condition. This hoop stress results directly from the radial flow of the interstitial fluid in the cartilage layer.

Biomechanical Phenomena↗

Experimentally Induced Articular Cartilage Injury: The Combined Use of Misoprostol and Diclofenac as Therapeutic Agents.

Injection of chymopapain (CP) into the rabbit knee causes rapid depletion of proteoglycans (PGs) in the articular cartilage. Successful repair of the articular cartilage follows injection of only 0.2 mg CP whereas in animals injected with 0.2 mg CP, the repair phase fails leading to cartilage destruction within 21 days. Previous work by the authors indicated that daily oral diclofenac reduced the severity and incidence of CP-induced cartilage injury after 21 days. The present study was designed to determine if administration of diclofenac promoted articular cartilage repair after CP injury over a longer period of time and if coadministration with misoprostol could reduce the concentration of diclofenac needed to promote repair as well as confer protection to the gastric mucosa. Adolescent male New Zealand white rabbits received CP-induced cartilage injury (2.0 mg) followed by daily oral diclofenac, diclofenac/misoprostol or misoprostol. Control animals received diclofenac, diclofenac/misoprostol, or misoprostol or no drug treatment with no cartilage injury. All animals were sacrificed after 2 months. Examination of the stomachs from animals receiving no drug or misoprostol only were completely normal. Most animals receiving diclofenac only had abnormal gastric mucosa. In contrast, coadministration of diclofenac/misoprostol revealed significantly fewer abnormalities. Analysis of the composite histologic score of patellae and measurements of cartilage PG content revealed no significant differences in groups which received CP injury with and without drug treatment. Histology scores and cartilage PG content from animals in groups which did not receive CP injury, but were treated with diclofenac/misoprostol, diclofenac or misoprostol were within normal limits and thus did not differ significantly from untreated control cartilage. The results of this study indicate that daily administration of diclofenac, diclofenac/misoprostol or misoprostol has no protective effect on CP-induced cartilage injury after 2 months. Administration of diclofenac only results in severe gastric abnormalities which are significantly reduced if diclofenac is coadministered with misoprostol. Administration of diclofenac, diclofenac/misoprostol or misoprostol has no effect on PG content of cartilage from otherwise normal joints.

Journal Article↗

Histochemical studies of the extracellular matrix of human articular cartilage--a review.

OBJECTIVE: This paper reviews the histochemistry of the extracellular matrix of human articular cartilage. No systematic review of histochemical knowledge and techniques in the study of articular cartilage has been published previously. METHODS AND RESULTS: Literature was searched in the Winspirs Medline database from 1960 to 2000. Only techniques applicable for bright field or polarization microscopy were considered. Unless otherwise noted, all applies to hyaline cartilage. The most widely used fixatives are adequate for routine staining of proteins, but proteoglycan fixation is problematic, and no one fixative can be recommended. Proteoglycan can be stained reliably but it is problematic that, at low substrate concentrations, these methods are not stoichiometric. Collagen can be stained efficiently, although attempts to differentiate collagen types have not been successful. CONCLUSIONS: Detailed studies of fixation and staining procedures should be carried out and standards for cartilage sampling, handling and evaluation agreed upon if results from different laboratories are to be compared.

Cartilage, Articular↗

Resurfacing potential of heterologous chondrocytes suspended in fibrin glue in large full-thickness defects of femoral articular cartilage: an experimental study in the goat.

A large full-thickness articular-cartilage defect was created in the medial femoral condyle of 32 adult goats. The defects were xenografted with isolated rabbit chondrocytes suspended in fibrin glue. Sham operated goats, where only a standardized defect was created, were used as controls. Results of cartilage repair were assessed after 3, 8, 13, 26 and 52 weeks. The repair tissue was evaluated macroscopically, histologically and biochemically. Results indicated that xenografted rabbit chondrocytes survived the transplantation and maintained their potential to produce matrix in fibrin glue, particularly if they were located in a non-weight-bearing area. In terms of an immunological reaction to xenografted chondrocytes, only mild signs of synovitis were observed in both groups and rejection of transplanted cells did not occur. From 3 weeks gradually progressive resolvement of the fibrin glue was observed with subsequent replacement by fibrous tissue. Initially xenografted defects histologically showed better tendency for cartilage regeneration, however, 52 weeks after surgery no significant differences could be detected in the repair tissue of both groups macroscopically, histologically and on biochemical scoring. The amount of collagen type II in the newly synthesized matrix was 75% 1 year after surgery. This study shows that isolated heterologous chondrocytes can be used for transplantation in articular cartilage defects, however, fibrin glue does not offer enough biomechanical support to the cells to maintain its function as a three-dimensional scaffold.

Animals↗

The biological effect of continuous passive motion on the healing of full-thickness defects in articular cartilage. An experimental investigation in the rabbit.

A new concept, continuous passive motion of a synovial joint in vivo, was investigated to determine its biological effect on the healing of full-thickness articular cartilage defects that penetrate the subchondral bone of knee joints of adolescent and adult rabbits. The effect of continuous passive motion was compared with the effects of immobilization and of intermittent active motion. This investigation included assessment of 480 defects in the knees of 120 adolescent rabbits and assessment of 108 defects in the knees of twenty-seven adult rabbits. The continuous passive motion was well tolerated by these animals, whose general well-being was undisturbed. The healing of the defects at weekly intervals up to four weeks was assessed by gross examination and by an analysis of two indices of healing determined by light microscopy: (1) the nature of the reparative tissue, and (2) the degree of metachromasia of the matrix as demonstrated by toluidine-blue staining. At three weeks this assessment revealed that in the adolescent rabbits, healing of the defects by hyaline articular cartilage was present in 8 per cent of forty defects in ten animals whose knees were immobilized, in 9 per cent of forty defects in ten animals whose knees were permitted intermittent active motion, and in 52 per cent of forty defects in ten animals whose knees were managed immediately after operation by continuous passive motion. At three weeks, in the adult animals, healing of the defects by hyaline articular cartilage was present in 3 per cent of thirty-six defects in nine animals whose knees were immobilized, in 5 per cent of thirty-six defects in nine animals whose knees were permitted intermittent active motion, and in 44 per cent of thirty-six defects in nine animals whose knees were managed immediately after operation by continuous passive motion. Thus, the metaplasia of the healing tissue within the defects from undifferentiated mesenchymal tissue to hyaline articular cartilage was not only much more rapid but also much more complete with continuous passive motion than with either immobilization or intermittent active motion.

Age Factors↗

MR imaging of articular cartilage at 1.5T and 3.0T: comparison of SPGR and SSFP sequences.

OBJECTIVE: To compare articular cartilage signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and thickness measurements on a 1.5 T and a 3.0 T magnetic resonance (MR) scanner using three-dimensional spoiled gradient recalled echo (3D-SPGR) and two 3D steady-state free precession (SSFP) sequences. METHODS: Both knees of five volunteers were scanned at 1.5 T and at 3.0 T using a transmit-receive quadrature extremity coil. Each examination consisted of a sagittal 3D-SPGR sequence, a sagittal fat suppressed 3D-SSFP (FS-SSFP) sequence, and a sagittal Dixon 3D-SSFP sequence. For quantitative analysis, we compared cartilage SNR and CNR efficiencies, as well as average cartilage thickness measurements. RESULTS: For 3D-SPGR, cartilage SNR efficiencies at 3.0 T increased compared to those at 1.5 T by a factor of 1.83 (range: 1.40-2.09). In comparison to 3D-SPGR, the SNR efficiency of FS-SSFP increased by a factor of 2.13 (range: 1.81-2.39) and for Dixon SSFP by a factor of 2.39 (range: 1.95-2.99). For 3D-SPGR, CNR efficiencies between cartilage and its surrounding tissue increased compared to those at 1.5 T by a factor of 2.12 (range: 1.75-2.47), for FS-SSFP by a factor 2.11 (range: 1.58-2.80) and for Dixon SSFP by a factor 2.39 (range 2.09-2.83). Average cartilage thicknesses of load bearing regions were not different at both field strengths or between sequences (P>0.05). Mean average cartilage thickness measured in all knees was 2.28 mm. CONCLUSION: Articular cartilage imaging of the knee on a 3.0 T MR scanner shows increased SNR and CNR efficiencies compared to a 1.5 T scanner, where SSFP-based techniques show the highest increase in SNR and CNR efficiency. There was no difference between average cartilage thickness measurements performed at the 1.5 T and 3.0 T scanners or between the three different sequences.

Adult↗

Protocol issues for delayed Gd(DTPA)(2-)-enhanced MRI (dGEMRIC) for clinical evaluation of articular cartilage.

Biochemical and histologic data have validated the technique of delayed gadolinium-enhanced MRI, in which the T(1) values of cartilage after penetration of Gd(DTPA)2-allow assessment of the glycosaminoglycan (GAG) component of articular cartilage. This work describes the factors that have been found to be important for the practical implementation of the technique: 1) Exercise immediately after intravenous contrast administration was necessary for effective penetration of the contrast into the articular cartilage; 2) double-dose contrast was better than single-dose; 3) after contrast administration, a time window of 30-90 min for the hip, and 2-3 hr for all compartments of the knee proved to be appropriate for assessing articular cartilage; and 4) in some cases of hypointensities in the subchondral patellar bone, decreased penetration of the contrast agent into cartilage from bone was found. With the protocol described, ROIs on T(1) images were reproducible within 15% on two separate imaging sessions, and initial clinical studies demonstrated the possible applications of the technique. Magn Reson Med 45:36-41, 2001.

Cartilage, Articular↗