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Modification of articular cartilage and subchondral bone pathology in an ovine meniscectomy model of osteoarthritis by avocado and soya unsaponifiables (ASU).

OBJECTIVE: To examine the effect of an oral preparation of avocado and soya unsaponifiables (ASU) on the development of joint pathology in an ovine model of osteoarthritis (OA), using computer-assisted histomorphometric methods. DESIGN: OA was induced in ovine knee joints by bilateral lateral meniscectomy (N=32). ASU (900 mg/weekday) was given orally to half the group (MenX+ASU), the remainder receiving placebo (MenX). Sixteen animals were used as non-operated controls (NOC). At 3 and 6 months post-meniscectomy, histological sections from the medial and lateral femoral condyles (MFC, LFC), tibial plateaux (MTP, LTP) and trochlear groove (TG) were prepared from all joints. Sections were scored using traditional histopathological scales, and computerized image analysis, measuring total cartilage area, uncalcified cartilage (UCC) and subchondral bone plate (SCP) thickness, and intensity of articular cartilage toluidine blue staining (mean greyscale intensity, black=255) as an index of proteoglycan (PG) content. RESULTS: Computerized image analysis showed significant histological differences not detectable by traditional scoring methods. ASU-treated animals at 6 months showed reduced loss of toluidine blue stain in the MTP (P=0.015) and LTP (P=0.001), and significantly greater staining in the TG than either placebo or NOC groups (P=0.011). UCC thickness increased after meniscectomy, but tended to be highest in ASU-treated animals, significantly so in the middle zone of the LFC (MenX+ASU: 1.03+/-0.21mm vs MenX: 0.79+/-0.14 mm, P=0.018; NOC: 0.77+/-0.17 mm). Lateral compartment SCP thickness increased post-meniscectomy but was increased significantly less in the inner zone of the LTP in ASU-treated sheep (MenX+ASU: 1.37+/-0. 23 mm vs MenX: 1.68+/-0.28 mm, P=0.033; NOC=1.22+/-0.33 mm). CONCLUSIONS: In this model ASU treatment following meniscectomy appeared to confer a subtle but statistically significant protective effect on articular cartilage. Although the drug failed to prevent focal cartilage lesions, characteristic of this model, histomorphometric analysis demonstrated greater PG content and UCC thickness in adjacent joint regions of ASU-treated animals. In addition, a statistically significant reduction of subchondral bone sclerosis was noted in the LTP region of the drug-treated group. An anabolic effect on chondrocytes, resulting in the stimulation of matrix production in regions distant to the insult, was also suggested by the data. These findings support other studies which have proposed that ASU may exhibit disease-modifying anti-OA activity.

Animals↗

Chondrocyte deformation and local tissue strain in articular cartilage: a confocal microscopy study.

It is well accepted that mechanical forces can modulate the metabolic activity of chondrocytes, although the specific mechanisms of mechanical signal transduction in articular cartilage are still unknown. One proposed pathway through which chondrocytes may perceive changes in their mechanical environment is directly through cellular deformation. An important step toward understanding the role of chondrocyte deformation in signal transduction is to determine the changes in the shape and volume of chondrocytes during applied compression of the tissue. Recently, a technique was developed for quantitative morphometry of viable chondrocytes within the extracellular matrix using three-dimensional confocal scanning laser microscopy. In the present study, this method was used to quantify changes in chondrocyte morphology and local tissue deformation in the surface, middle, and deep zones in explants of canine articular cartilage subjected to physiological levels of matrix deformation. The results indicated that at 15% surface-to-surface equilibrium strain in the tissue, a similar magnitude of local tissue strain occurs in the middle and deep zones. In the surface zone, local strains of 19% were observed, indicating that the compressive stiffness of the surface zone is significantly less than that of the middle and deep zones. With this degree of tissue deformation, significant decreases in cellular height of 26, 19, and 20% and in cell volume of 22, 16, and 17% were observed in the surface, middle, and deep zones, respectively. The deformation of chondrocytes in the surface zone was anisotropic, with significant lateral expansion occurring in the direction perpendicular to the local split-line pattern. When compression was removed, there was complete recovery of cellular morphology in all cases. These observations support the hypothesis that deformation of chondrocytes or a change in their volume may occur during in vivo joint loading and may have a role in the mechanical signal transduction pathway of articular cartilage.

Animals↗

Comparison of multislice CT arthrography and MR arthrography for the detection of articular cartilage lesions of the elbow.

The objective of this study was to compare the value of multislice CT arthrography and MR arthrography in the assessment of cartilage lesions of the elbow joint. Twenty-six cadaveric elbow specimens were examined with the use of CT arthrography and MR arthrography prior to joint exploration and macroscopic inspection of articular cartilage. Findings at CT and MR arthrography were compared with macroscopic assessments in 104 cartilage areas. At macroscopic inspection, 45 cartilage lesions (six grade 2 lesions, 25 grade 3 lesions, 14 grade 4 lesions) and 59 areas of normal articular cartilage were observed. With macroscopic assessment as the gold standard CT and MR arthrography showed an overall sensitivity/specificity of 80/93% and 78/95% for the detection of cartilage lesions, respectively. Only two of six grade 2 lesions were detected by CT and MR arthrography. For the diagnosis of grade 3 and 4 lesions, the sensitivity/specificity was 87/94% with CT arthrography, and 85/95% with MR arthrography. In an experimental setting multislice CT arthrography and MR arthrography showed a similar performance in the detection of cartilage lesions. Both methods indicated limited value in the diagnosis of grade 2 articular cartilage lesions.

Aged↗

Mechanical effects of the intraarticular administration of high molecular weight hyaluronic acid plus phospholipid on synovial joint lubrication and prevention of articular cartilage degeneration in experimental osteoarthritis.

OBJECTIVE: To examine in vivo the effects of a mixture of high molecular weight hyaluronic acid (HA) plus phospholipids on joint lubrication and articular cartilage degeneration. METHODS: Experimental osteoarthritis (OA) of the right knee was induced by anterior cruciate and medial collateral ligament transection in 40 rabbits. The animals were subjected to 8 consecutive weekly intraarticular administrations of high molecular weight HA (the HA200 group), conventional molecular weight HA (the HA80 group), or high molecular weight HA plus L-delta dipalmitoyl phosphatidylcholine liposomes (the PHA group) and were killed 1 week after the final injection. The remaining transected right knees (the OA group) and randomly selected nontransected contralateral left knees (the control group) were collected simultaneously. Each group (n = 10) was divided into 2 equal subgroups, one of which was evaluated histologically while the other was subjected to a lubricating ability test using a pendulum friction tester. RESULTS: The injected knees had a tendency to demonstrate less damage to the articular cartilage compared with the OA group, and the histologic findings in all groups except for the PHA group differed significantly from the control group. There was a significant difference in the mean +/- SD friction coefficient between the control group (0.0100 +/- 0.00300) and the OA (0.0206 +/- 0.00649), HA200 (0.0190 +/- 0.00427), and HA80 (0.0177 +/- 0.00712) groups (P < 0.05 for each comparison), but not between the control group and the PHA group (0.0150 +/- 0.00330) (P = 0.15). CONCLUSION: To our knowledge, this is the first in vivo study to examine whether intraarticular injections of phospholipids influence joint lubrication by acting as a boundary lubricant, thus protecting articular cartilage from degenerative changes.

Animals↗

Inhibition of interleukin-1-induced synovitis and articular cartilage proteoglycan loss in the rabbit knee by recombinant human interleukin-1 receptor antagonist.

Intra-articular injection of interleukin-1 (IL-1) into the knee joints of rabbits produces a synovitis associated with the loss of proteoglycan from the matrix of articular cartilage. This experimental finding supports the hypothesis that IL-1 is a possible mediator of the pathology of inflammatory joint diseases and suggests that antagonism of IL-1 could offer a therapeutic approach to these diseases. It has recently been reported that culture of human monocytes on adherent IgG stimulates these cells to synthesize a specific inhibitor of IL-1 bioactivity (IL-1ra) that acts as a receptor antagonist with lymphocytes and mesenchymal cells. We have now shown that intravenous injection of IL-1ra into rabbits given an intra-articular injection of recombinant IL-1 beta not only inhibits the entry of leukocytes into the synovial lining and joint cavity but blocks the ability of IL-1 to cause loss of proteoglycan from articular cartilage. This ability of IL-1ra to inhibit IL-1-induced arthritis in the rabbit reveals that this protein has appropriate pharmacokinetic and pharmacodynamic properties and further strengthens the belief that it may be a useful therapeutic agent.

Animals↗

Transplantation of free perichondrial grafts into rabbit articular cartilage is associated with matrix vesicle calcification.

Autogenous perichondrial grafts from rabbit ear were transplanted into articular cartilage defects in the knee joint. Electron micrographs performed after 2 months revealed calcifications associated with cartilaginous-forming cells and extracellular matrix vesicles. Many of these vesicles contained apatite crystals, particularly in areas adjacent to the calcifying fronts. In these areas the vesicular membrane was occasionally ruptured by the crystals. Many crystals in the calcifying front proper were organized alongside collagen fibers. Examination of sham-operated and normal controls revealed the occurrence of non-calcifying matrix vesicles. The results of the present and previous studies suggest that matrix vesicles occur in normal articular cartilage in a latent form, their calcification being associated with changes of the metabolic state of the tissue.

Animals↗

Degradation of bovine articular cartilage proteoglycans in vitro. The effect of Bacteroides gingivalis.

The black-pigmented Bacteroides gingivalis has previously been isolated from periodontal pockets and been shown capable of inflicting advanced tissue damage. Its effect on the degradation of articular cartilage proteoglycans has not previously been known. In these experiments it was demonstrated that under aerobic conditions the anaerobic microbe B. gingivalis is very potent in degrading the proteoglycans of fresh articular cartilage. It is even more potent in the presence of fetal calf serum (FCS) than in its absence. When the cartilage has been frozen/thawed there is still a slight enhancement of the degradation by B. gingivalis, but when the cartilage has been devitalized and de-enzymed by heat, the cartilage-degrading capacity of B. gingivalis is totally abolished. However, addition to the cartilage cultures of filtered conditioned medium from B. gingivalis inhibits in some degree the degradation of articular cartilage proteoglycans. It is therefore suggested that the great cartilage-degrading ability of Bacteroides gingivalis shown in this culture system could be due to its ability to degrade proteinase inhibitors.

Animals↗

Effect of loading and prednisolone treatment on the glycosaminoglycan content of articular cartilage in dogs.

The effect of prolonged prednisolone administration on glycosaminoglycan components was studied by means of determinations of galactosamine, glucosamine, uronic acid, sulphate and sialic acid content in normally loaded and spared articular cartilages of the knee-joints in dogs. After 40 days, all glycosaminoglycan components decreased by 58% in the spared cartilage, as compated with the controls. Prolonged administration of 0.5 mg prednisolone/kg body weight (corresponding to a low therapeutic dose), elicited a further decrease in galactosamine, whereas the other components remained practically unchanged. In the normally loaded articular cartilage of prednisolone-treated dogs the glycosaminoglycan components decreased by about 11-31% compared with untreated controls. The quantitative data indicate that in the changes occurring the glycosaminoglycan composition of the articular cartilage due to relief of function and to prednisolone treatment, chondroitin suplphate is mainly involved. The changes due to prednisolone treatment are dependent on the functional demand of the joint.

Animals↗

Survival of articular cartilage after controlled impact.

Survival characteristics of forty-three specimens of living human bone and articular cartilage from the knees of eight renal-transplant donors were studied, using a drop-tower device. Autoradiography and light and scanning electron microscopy revealed no evidence of chondrocyte death or structural damage until stress levels of twenty-five newtons per square millimeter were reached, corresponding to strains on the order of 20 to 30 per cent and involving energy absorption of one millijoule per cubic millimeter. The data for strain rates of 500 and 1000 s-1 suggest that impact loads sufficient to fracture a femoral shaft of an automobile occupant are nearly sufficient to cause chondrocyte death and fissuring in the articular cartilage of either the knee or the hip if the load-bearing areas measure less than 500 square millimeters.

Autoradiography↗

The relationship between articular cartilage degeneration and bone changes of the first metatarsophalangeal joint.

Plain-film radiography is commonly used in the assessment of joints affected by osteoarthritis. It has been shown that the condition of articular cartilage in the knee, when grossly assessed, does not always correlate well to the radiographic evaluation of the joint. The aim of this study was to determine whether a relationship existed between the radiographic appearance of the subchondral bone and the morphological condition of the articular cartilage surfaces of the first metatarsophalangeal joint. Forty-nine pairs of cadaveric metatarsals and their respective proximal phalanges were studied in order to determine the correlation between articular cartilage degeneration and radiographic grade using a modified Kellgren-Lawrence scale. The relationship between cartilage degeneration and age, gender, osteophytes, metatarsal length, and measured angles (proximal articular set angle, distal articular set angle, intermetatarsal angle) was also investigated. It was found that there was a significant correlation between radiographic grade and cartilage degeneration on both the metatarsal head and the base of the proximal phalange (r2 = .2038 and .1733, respectively). However, while useful in the clinical setting, bony changes of the first metatarsophalangeal joint, as seen radiographically, fail to provide a full representation of the level of cartilage degeneration on the articular surfaces of this joint.

Adult↗

Induction of interleukin-1 in articular cartilage by explantation and cutting.

OBJECTIVE: To investigate the effect of explantation and fine cutting of articular cartilage upon intracellular inflammatory signaling pathways and expression of interleukin-1 (IL-1). METHODS: Cartilage from porcine metacarpophalangeal joints was cultured in serum-free medium. Tissue extracts were examined for ERK activation by phosphorylated-Western blotting, for JNK and p38 MAPK activity by kinase assay, and for IkappaBalpha. IL-1alpha and IL-1beta messenger RNA (mRNA) was measured by reverse transcriptase-polymerase chain reaction. IL-1 activity was measured by the induction of serum amyloid A protein in cultured chondrocytes. RESULTS: All 3 MAPKs (p38, JNK, and ERK) were rapidly activated upon dissection and explantation of the cartilage. IL-1alpha and IL-1beta mRNA was also induced: the speed and magnitude of induction were increased if the explants had been finely cut. IL-1 activity that could be inhibited by IL-1 receptor antagonist or antibodies to IL-1alpha was found in extracts of explants cultured for 20 hours or lysates of cells isolated from them. This activity was likely due to intracellular proIL-1alpha that was not secreted. ProIL-1beta would not be detected because it is biologically inactive. The mechanism of inflammatory signaling pathway activation underlying the induction of IL-1 is unknown. CONCLUSION: Explantation and cutting of articular cartilage activates intracellular inflammatory signaling pathways and induces expression of mRNA for IL-1alpha and IL-1beta. Biologically active IL-1alpha protein was detectable in cartilage lysates and was probably intracellular proIL-1alpha. We were unable to show that IL-1 was secreted by chondrocytes.

Animals↗

The effects of ketorolac and morphine on articular cartilage and synovium in the rabbit knee joint.

Analgesics are commonly injected intra-articularly for analgesia after arthroscopic surgery, especially of knee joints. The aim of this study was to research the effects of ketorolac and morphine on articular cartilage and synovial membrane. This study used rabbit right and left hind knee joints. The treatments, saline, morphine, or ketorolac, were administered intra-articularly 24 h after injection, and 5 joints from animals in each drug group were chosen randomly to form Group I and subgroups of Group I. The same procedures were applied after 48 h and 10 days of injection to form Groups II and III, respectively, and subgroups of these groups. Knee joints were excised and a blinded observer evaluated the histopathology according to inflammation of the articular cartilage, inflammatory cell infiltration, hypertrophy, and hyperplasia of the synovial membrane. No histopathological changes were found in the control groups. In the ketorolac and morphine groups, there were varying degrees of synovial membrane inflammatory cell infiltration and minimal, mild, or moderate synovial membrane cell hyperplasia or hypertrophy. Except for the ketorolac group at 24 h, both ketorolac and morphine groups showed more histopathological changes than controls (p < 0.05). Morphine and ketorolac both cause mild histopathological changes in rabbit knee joints, morphine causing more than ketorolac, but both of the drugs can be used intra-articularly with safety.

Analgesics, Opioid↗

Zone-specific cell biosynthetic activity in mature bovine articular cartilage: a new method using confocal microscopic stereology and quantitative autoradiography.

A new methodology was developed to measure spatial variations in chondrocyte/matrix structural parameters and chondrocyte biosynthetic activity in articular cartilage. This technique is based on the use of a laser scanning confocal microscope that can "optically" section chemically fixed, unembedded tissue. The confocal images are used for morphometric measurement of stereologic parameters such as cell density (cells/mm3), cell volume fraction (%), surface density (l/cm), mean cell volume (micron3), and mean cell surface area (micron2). Adjacent pieces of tissue are simultaneously processed for conventional liquid emulsion autoradiography, and a semiautomated grain counting program is used to measure the silver grain density at regions corresponding to the same sites used for structural measurements. An estimate of chondrocyte biosynthetic activity in terms of grains per cell is obtained by dividing the value for grain density by that for cell density. In this paper, the newly developed methodology was applied to characterize the zone-specific behavior of adult articular cartilage in the free-swelling state. Cylinders of young adult bovine articular cartilage were labelled with either [3H]proline or [35S]sulfate, and chondrocyte biosynthesis and structural parameters were measured from the articular surface to the tidemark. The results showed that chondrocytes of the radial zone occupied twice the volume and surface area of the chondrocytes of the superficial zone but were 10 times more synthetically active. This efficient and unbiased technique may prove useful in studying the correlation between mechanically induced changes in cell form and biosynthetic activity within inhomogeneous tissue as well as metabolic changes in cartilage due to ageing and disease.

Animals↗

Articular cartilage of knee: normal patterns at MR imaging that mimic disease in healthy subjects and patients with osteoarthritis.

PURPOSE: To evaluate normal magnetic resonance (MR) imaging findings that may mimic articular cartilage diseases in healthy subjects and patients with osteoarthritis of the knee. MATERIALS AND METHODS: Sagittal fat-suppressed intermediate-weighted fast spin-echo (FSE) (repetition time msec/echo time [TE] msec, 4,000/13), sagittal T2-weighted FSE (4,000/39), and sagittal fat-suppressed three-dimensional (3D) spoiled gradient-echo (SPGR) (60/5, 40 degrees flip angle) MR images were acquired in 28 patients and four volunteers. FSE images with a TE of 13 msec were considered "short-TE images"; those with a TE of 39 msec were considered "long-TE images." Presence of normal MR imaging appearance of articular cartilage was determined by one author. Contrast between cartilage and adjacent structures (meniscus, joint capsule, synovial fluid, muscle) was calculated in posterior regions of the femoral condyle on images obtained with each sequence; Wilcoxon signed rank testing was performed. RESULTS: The following appearances were observed in patients with knee osteoarthritis (on short-TE FSE, long-TE FSE, and SPGR MR images, respectively): (a) ambiguity of surface contour in posterior region of the femoral condylar cartilage (in zero, zero, and 20 patients), (b) linear area of high signal intensity in deep zone adjacent to subchondral bone of femoral condyle (in zero, zero, and 26 patients), (c) pseudolaminar appearance in posterior region of femoral condylar cartilage (in seven, nine, and 24 patients), (d) truncation artifact in patellofemoral compartment (in seven, six, and 27 patients), (e) susceptibility artifact on cartilage surface caused by air or metal (in three, three, and 11 patients), (f) decreased signal intensity in distal part of trochlear cartilage (in 28, 28, and 28 patients), (g) cartilage thinning adjacent to the anterior horn of the lateral meniscus (in 19, 19, and 21 patients), and (h) focal cartilage flattening in posterior region of femoral condyle (in 16, 16, and nine patients). Cartilage-meniscus and cartilage-synovial fluid contrast was significantly higher on fat-suppressed FSE than on fat-suppressed 3D SPGR MR images (P <.001). CONCLUSION: Fat-suppressed FSE and 3D SPGR MR images showed nonuniform signal intensity arising from articular cartilage and cartilage thinning, both of which could mimic disease.

Adult↗

[Repair of large articular cartilage defect of hip with allograft of skull periosteum].

It is very difficult to repair large articular cartilage defect of the hip. From May 1990 to April 1994, 47 hips in 42 patients of large articuler cartilage defects were repaired by allograft of skull periosteum. Among them, 14 cases, whose femoral heads were grade. IV necrosis, were given deep iliac circumflex artery pedicled iliac bone graft simultaneously. The skull periosteum had been treated by low tempreturel (-40 degrees C) before and kept in Nitrogen (-196 degrees C) till use. During the operation, the skull periosteum was sutured tightly to the femoral head and sticked to the accetabulum by medical ZT glue. Thirty eight hips in 34 patients were followed up for 2-6 years with an average of 3.4 years. According to the hip postoperative criteria of Wu Zhi-kang, 25 cases were excellent, 5 cases very good, 3 cases good and 1 case fair. The mean score increased from 6.4 before operation to 15.8 after operation. The results showed, in compare with autograft of periosteum for biological resurface of large articular defect, this method is free of donor-site morbidity. Skull periosteum allograft was effective for the treatment of large articular cartilage defects in hip.

Adolescent↗

Histologic changes in articular cartilage after medial meniscus replacement in rabbits.

PURPOSE: Meniscal allografts show capsular ingrowth, but it remains to be established whether meniscal transplantation can prevent long-term degeneration of articular cartilage. This study examined whether immediate or delayed transplantation of the medial meniscus can protect the knee from degenerative changes. TYPE OF STUDY: Experimental study. METHODS: Thirty-five rabbits were divided into 5 groups. Three rabbits developed infective arthritis and were excluded from the study. Group A (6 animals) and group C (6 animals) had meniscectomy only; group B (7 animals) and group D (6 animals) underwent meniscal transplantation immediately after meniscectomy; group E (7 animals) had delayed transplantation 6 weeks after meniscectomy. Six nonoperated knees served as controls. Histologic changes of the articular cartilage were examined 6 weeks (groups A, B) and 1 year (groups C, D, E, controls) after surgery. RESULTS: All operated groups showed more histologic changes than the control group (P < .00001 for both the medial tibial plateau and medial femoral condyle in all groups). At 6 weeks follow-up, no differences were found between the postmeniscectomy group and the transplanted group. At 1 year, immediately transplanted knees showed less degenerative changes than meniscectomized knees (P < .0001 for medial tibial plateau and P < .005 for medial femoral condyle). Delayed transplantation resulted in more degenerative changes than both meniscectomy only and immediate transplantation (for both comparisons, P < .00001 for both medial tibial plateau and medial femoral condyle). CONCLUSIONS: Immediate meniscal transplantation in rabbits has a protecting effect on articular cartilage for the long-term whereas delayed transplantation leads to even more degenerative changes than meniscectomy only. CLINICAL RELEVANCE: If these results are applicable to humans, they would support immediate, not delayed, transplantation after removal of a meniscus.

Animals↗