Topographic variation in biglycan and decorin synthesis by articular cartilage in the early stages of osteoarthritis: an experimental study in sheep

From October 1988 to January 1992, nine isolates of Pseudomonas aeruginosa carrying transferable plasmids encoding imipenem-hydrolyzing beta-lactamase (pI = c. 9.5) were recovered from nine different patients in a neurosurgical ward of a hospital in Japan. The beta-lactamase activities of the sonicated extracts from the transconjugants were inhibited by EDTA and this was partially reversible by the addition of zinc cation. The substrate specificity and pI of the beta-lactamase were similar to those of the metallo beta-lactamases from P. aeruginosa and Serratia marcescens TN9106. All strains were resistant to imipenem, carbenicillin and antipseudomonal cephems including ceftazidime, cefsulodin, cefpirome, while four and five strains were susceptible to piperacillin and aztreonam, respectively. Both low level imipenem resistance and high level cephem resistance were co-transferred with the production of metallo beta-lactamase, while resistance to piperacillin, aztreonam, and high level imipenem-resistance were not selected. Production of chromosomal cephalosporinase in piperacillin resistant strains was derepressed, and production of outer membrane protein of D2 was diminished in highly imipenem resistant strains. Six strains were isolated in 1991, and the amounts of antipseudomonal agents, especially imipenem, used in the neurosurgical ward increased markedly in this year. Only three of the nine isolates had the same serotype, pyocin type and phage type. Our results suggest that the repeated isolation of imipenem and cephem-resistant P. aeruginosa producing metallo beta-lactamase was related to the high usage of antipseudomonal beta-lactam antibiotics such as imipenem, and was exacerbated by the dissemination of a plasmid.     

Loss of decorin from the surface zone of articular cartilage in a chick model of osteoarthritis

The objective of this study was to immunolocalize decorin and to assess changes as a result of pyridoxine (PN) deficiency in chick articular cartilage from femoral condyles. After maintenance on a normal diet for the first two weeks after hatching, 15 broiler chickens were deprived of this vitamin for 6 weeks. It was previously shown that the ankle joints of PN-deficient animals are swollen with effusions. They also present an abnormal gait, enlarged bony margins, and fissuring of the articular cartilages. Milder changes (no fissures) were also shown in the knee joints. Data from a previous study were suggestive that sulfated glycosaminoglycans are lost from the knee cartilage surface into synovial fluid. The current study was focused on the small proteoglycan, decorin, which coats the surface of collagen fibrils and may regulate their morphology. To examine decorin in normal and PN-deficient articular cartilage, a monoclonal antibody to an epitope on the protein core of decorin was used for immunohistochemical staining of tissue sections and for Western Blot analysis of cartilage extracts. Reduction of staining with the antibody was demonstrated in the tangential surface zone of PN-deficient cartilage, and Western Blot analysis showed reduced intensity of decorin bands compared to normal controls. These data suggest that a lack of decorin may play a role in the enlargement of collagen bundles in the tangential zone of PN-deficient articular cartilage as observed in a previous electron microscopic study.     

The effect of intersegmental knee moments on patellofemoral contact mechanics in cycling

The aim of this study was to evaluate the effect of bicycle pedal design on the mechanics of the patellofemoral joint. Previous research determined that for certain riders the non-driving varus and internal knee moments could be reduced by switching from fixed to free floating pedals (Ruby and Hull, 1993). It was postulated that the presence of varus and internal knee moments during fixed pedal cycling may adversely affect patellofemoral joint contact mechanics which could lead to the development of anterior knee pain. To investigate the effect of pedal design the hypothesis that varus and internal intersegmental knee moments significantly increase patellofemoral contact pressure, contact area and contact force was tested. To test this hypothesis cycling loads were simulated in vitro using a six-degree-of-freedom load application system (LAS). Using the LAS, varus moments ranging from 0-20 Nm and internal knee moments ranging from 0-10 Nm were applied simultaneously with quadriceps force at knee flexion angles of 60 and 90 degrees. Patellofemoral contact patterns were measured using pressure sensitive film. An applied 10 Nm internal moment significantly increased both contact area by 16% and contact force by 22% at 90 of flexion. The application of a 20 Nm varus moment modestly yet significantly increased contact area by 6% and contact force by 5%. When applied in combination, varus and internal knee moments increased contact area and force by as much as 29% and 28% respectively. The mean contact pressure was not significantly increased by either of the two moments. The results suggest that non-driving intersegmental knee moments subject the patellofemoral joint to loads and contact patterns which may accelerate the development of chondromalacia.     

Membrane transport properties of bovine articular cartilage

The thermodynamic parameters which define transport of nonelectrolytes through bovine articular cartilage membranes were evaluated. H3HO, glucose and sucrose were used as permeants. These solutes permeate more readily through the upper layers (near the articular surface) than through the denser deeper layers approaching bone. Cartilage is similar in many respects to a swollen cellulose gel. Viscous-flow contributes importantly to transport within cartilage thus greatly enhancing the movement of nutrients.     

Assessment of articular cartilage and subchondral bone: subtle and progressive changes in experimental osteoarthritis using 50 MHz echography in vitro

The main objectives of this work were to demonstrate the potential of 50 MHz echography for assessing initial and progressive morphological and structural changes of articular cartilage and bone developed in an experimental model of osteoarthritis (OA). Degenerative lesions were induced in rat knees by the unilateral intra-articular injection of a 3 mg dose of mono-iodo-acetic acid. To assess the lesion progression, the animals (n = 30) were sacrificed at different time intervals up to 8 weeks after the injection. Three-dimensional echographic data were acquired in vitro on patellar cartilage and bone at various stages of the remodeling process using a scanning ultrasound microscope. Changes involving the OA cartilage characteristics are discussed relative to those of the contralateral control joint which received a placebo. Images of control cartilage showed a smooth hyperechoic articular surface and an echoic matrix. The cartilage thickness was 266 +/- 44 microns (mean +/- SD) in the central region of the tissue. The precision of ultrasonic thickness measurements was better than 1.3%. First changes in cartilage internal structure and subchondral bone appeared on ultrasound images 3 days after the injection and were even more evident by day 7. They resulted in a slight thinning of the cartilage, a 30% increase of its internal structure echogenicity, and the appearance of echoic zones in subchondral bone. Histologic findings confirmed chondrocyte depletion and degeneration, decrease of matrix proteoglycans, and fibrovascular connective tissue proliferation at the subchondral plate. Progressive and severe lesions at both bone and cartilage surface and internal structure were assessed and correlated to histologic features. These results show that high resolution echography is sensitive to subtle and progressive osteochondral remodeling. This technique has the potential to be used for intra-articular quantitative imaging and assessment of early changes in bone and cartilage structure associated with natural human disease.     

Treatment of articular cartilage defects in athletes: an analysis of functional outcome and lesion appearance

This article characterizes chondral injuries and reviews the results of microfracture treatment in high-level competitive and recreational athletes. Thirty-eight high-level and 140 recreational athletes completed functional questionnaires preoperatively and yearly postoperatively, recording symptoms, function, and activity level. Second-look arthroscopy tapes were available in 26 high-level and 54 recreational athletes. The mean follow-up for the high-level athletes was 3.7 +/- 1.4 years. Chondral defects averaged 223 +/- 180 mm2. Lesion size and follow-up were not significantly different in the recreational group. Functional questionnaire responses demonstrated significant improvements from the time of microfracture to final follow-up. Improvement in function and symptoms was similar for the competitive and recreational athletes.     

Growth profiles and articular cartilage characterization in a goat model of Legg-Calve-Perthes disease

Numerous animal species, including the goat, have been evaluated as potential models for human Legg-Calve-Perthes disease (LCPD). These models disrupt the vasculature of the femoral head, causing it to collapse, and therefore do not mimic all the clinical patterns of the human disease. Baseline data regarding the weight and femoral length in the growing goat are not available. This study characterized the goat's normal growth for comparison with that of humans. The growth aberrations in the proximal femur created by surgically ablating the capital physis were described and compared with the aberrations observed in human LCPD cases. Age, weight, and femoral length (test and control) data were obtained for goats approximately 1 to 14 months of age. At 4 months of age, a craniolateral surgical approach was used to expose the cranial lateral capital physis so that it could be cauterized. Postoperative radiographs were evaluated by graphic analysis to assess the resultant changes in the morphology of the proximal femur. The articular cartilage of the femoral head and acetabulum was evaluated mechanically, using indentation testing, to determine the apparent modulus of elasticity, and histopathologically regarding its thickness and proteoglycan content. The proximal femurs of goats and humans exhibit similar morphology and growth patterns. There was a positive correlation between age, weight, and femoral lengths in the goat. The surgical procedure was effective in ablating the capital femoral physis as indicated by shorter femoral lengths and fragmented, flattened, and mushroomed femoral heads. The histopathological data revealed that the articular cartilage was significantly thicker in the operated hip joints at the ventrocaudal and cranial acetabula and the dorsal and ventral femoral heads. The test cartilage exhibited significantly less positive staining for proteoglycans in the dorsocaudal and the cranial acetabula as well as the ventral femoral head. The apparent modulus of elasticity, of the test cartilage was significantly lower than the control value at the dorsocaudal acetabulum. These data show that the surgical procedure produced morphological changes that mimic those in human LCPD. The increased thickness of the articular cartilage of the LCPD femoral head may account for the articular degeneration observed in older patients with LCPD, as increased cartilage thickness is associated with decreased tissue quality.     

Regeneration of defects in articular cartilage with callus and cortical bone grafts. An experimental study

Luteal-phase estrogen and progesterone concentrations were measured every other day and used to monitor the corpus luteum activity. The patterns of estrogen and progesterone concentrations were compared relative to the day of endogenous human chorionic gonadotropin (hCG) detection (defined as the day of implantation). The relationship between estrogen and progesterone and hCG concentrations was studied in 71 viable pregnancies, 12 clinical abortions, five preclinical abortions and 84 non-pregnant cycles after IVF/ET. Although all patients received luteal-phase progesterone support (25-50 mg/ml), low late luteal-phase progesterone concentrations of < 30 ng/ml from day + 11 to day + 15 were found in 64 patients (17% of viable pregnancies, 33.3% of clinical abortions, 60% of preclinical abortions and 53.6% of non-pregnant cycles) day + 1 was the day of retrieval). Implantation always occurred before or on day + 13 and 86% of pregnant cycles implanted on day + 8 to day + 11. Viable pregnancies had significantly higher mean progesterone concentrations on day + 3 to day + 7 (pre-implantation) and on day + 9 to day + 15 (postimplantation) than those of non-pregnant cycles or abortions. On the day of implantation, the mean +/- standard of deviation of estrogen (pg/ml) and progesterone (ng/ml) levels for viable pregnancies, clinical abortion and preclinical abortions were 314 +/- 210, 40.5 +/- 25; 226.7 +/- 246, 48.7 +/- 31; and 39.6 +/- 24.5, 28.6 +/- 24.5, respectively. On the same day, 73.2% of viable pregnancies, 41.7% of clinical abortions, and 20% preclinical abortions had a progesterone concentration > 30 ng/ml; 73.2% of viable pregnancies, 41.7% of clinical abortions and 20% of preclinical abortions had an estrogen concentration > 100 pg/ml. Although not precluding implantation completely, late luteal-phase hormonal deficiencies may impair endometrial growth and might ultimately lead to failure or abnormal implantation. A viable pregnancy requires not only a functional corpus luteum in the early luteal phase to develop a receptive endometrium, but also a responsive corpus luteum in the late luteal phase to support pregnancy. The time of implantation is critical. Implantation that occurs before the demise of the corpus luteum will facilitate a normal pregnancy.     

Tenascin-C and the development of articular cartilage

In comparison to the vast literature on articular cartilage structure and function, relatively little is known about how articular cartilage forms during embryogenesis and is endowed with unique phenotypic properties, most notably the ability to persist and function throughout postnatal life. In this minireview, we summarize recent studies from our laboratory suggesting that the extracellular matrix protein tenascin-C is involved in the genesis and function of articular chondrocytes. These and other data have led us to propose that tenascin-C may be part of in vivo mechanisms whereby articular chondrocytes develop at the epiphysis of long bone models, remain functional throughout postnatal life, and avoid the endochondral ossification process undertaken by the bulk of chondrocytes located in the metaphysis and diaphysis of skeletal models.     

Assessment of donor cell and matrix survival in fresh articular cartilage allografts in a goat model

The long-term survival of allografts of articular cartilage has been proposed to be dependent on the survival of the cells that maintain the unique structural and material properties of the allograft. In this study, we assessed cell survival in 24 fresh articular cartilage allografts of the medial plateau in a Spanish-goat model. A DNA-probe technique was used to distinguish clearly between DNA from donor (allograft) and host cells. The intraarticular survival of viable allograft chondrocytes in the transplanted articular cartilage started to diminish as early as 3 weeks after transplantation; however, there was considerable variation in the amount of donor cell DNA detected in the allografts at 6 and 12 months following transplantation. This contrasts with our experience with fresh allografts of ligament, tendon, and meniscus, in which no donor DNA was detected 4 weeks after transplantation. DNA from host cells was present in all articular cartilage allografts, as evidenced by detectable unique host DNA patterns. Histological and histochemical assays showed that none of the transplants demonstrated normal structure and composition at 1 year after transplantation. The grafts in which large quantities of donor DNA were present appeared grossly superior to those with no or reduced remaining demonstrable donor DNA.     

Finite deformation biphasic material properties of bovine articular cartilage from confined compression experiments

In 1990, Holmes and Mow [Journal of Biomechanics 23, 1145-1156] developed a hyperelastic biphasic theory to describe finite deformation behaviors of articular cartilage. To date, however, no experimental finite deformation studies have been made to assess the ability of this constitutive model to describe its finite deformation behaviors (e.g. kinetic creep and stress-relaxation, and equilibrium responses). The objectives of this study are: (1) to investigate whether this hyperelastic biphasic theory can be used to curve-fit the finite deformation compressive stress-relaxation behavior of the tissue, and from this procedure, to calculate its material coefficients; and (2) to investigate whether the theory, together with the calculated material coefficients, can accurately predict the outcome of an independent creep experiment followed by cyclical loading of the tissue. To achieve these objectives, circular cylindrical cartilage plugs were tested in confined compression in both stress-relaxation and creep experiments. Results demonstrated that curve-fits of the stress-relaxation experiments produced nonlinear generalized correlation coefficients of r2 = 0.99 +/- 0.02 (mean +/- standard deviation); theoretical predictions of the creep test differed on average by 10.0% +/- 2.0% relative to experimental results. When curve-fitting the creep experiments as well, it was found that the permeability coefficients differed from those obtained from the stress-relaxation experiments (k0,cr = 2.2 +/- 0.8 x 10(-15) m4 N-1 s-1 and Mcr = 0.4 +/- 0.8 vs k0,sr = 2.7 +/- 1.5 x 10(-15) m4 N-1 s-1, and Msr = 2.2 +/- 1.0); these differences may be attributed to imprecisions in the curve-fitting procedure stemming from the low sensitivity of the stress-relaxation and creep behaviors to large variations of M in the permeability function. Advantages and limitations of this theoretical model are presented in the text.     

Investigation into the effects of proteins and lipids on the frictional properties of articular cartilage

The aim of this study was to investigate the effects of the proteins and the lipids on the frictional properties of articular cartilage in the mixed and boundary lubricating regimes. Bovine articular cartilage that had been treated to remove the lipids, and cartilage that had been treated to remove the proteins, from the surface layer were studied in order to investigate differences in their lubricating abilities. Tests were carried out on a sliding friction rig under contact pressures of 0.5 and 4 MPa. The results of the friction tests carried out under the 4 MPa contact pressure showed a slight increase in friction coefficient for both the lipid and the protein deficient cartilage when compared with the control cartilage. These differences were more apparent at the shorter loading times but none of the differences were found to be statistically significant. The tests at the lower contact pressure of 0.5 MPa showed that removing the lipids by washing the surface with detergent increased the friction coefficient at the shorter loading times but had no effect at the longer loading times. Digesting the cartilage with trypsin to remove the proteins from the surface layer had no effect on the friction coefficient at the shorter loading times but reduced the friction coefficient at the longer loading times. Both these results were confirmed with specimens that had both the lipids and the proteins removed from the surface layer.     

The fate of the articular cartilage in intracapsular fracture of the femoral neck (articular cartilage in femoral neck fracture)

The fate of the articular cartilage of the hip joint with intracapsular neck fracture was studied by histological, histochemical and autoradiographic techniques and by using a polarized microscope and a scanning electron microscope. Cartilage specimens from 93 femoral heads and 7 acetabula were obtained from fractured hips 2 days to 4 1/3 years postfracture and from control hips with various disorders. The cartilage degeneration appeared 2 weeks after fracture and advanced steadily with time. The matrix was covered, invaded and ultimately replaced by the fibrous tissue. Chondrocyte viability, though it was lost from the surface, was recognized in the deep matrix even in the oldest fracture examined. It is concluded that the humoral factor directly caused by the injury as well as the biomechanical impairment, i.e. a loss of physical stress, may play an essential role in the pathogenesis of the degeneration. The possibility of regeneration was discussed.     

Human joint performance and the roughness of articular cartilage

The Doppler technique has been used to evaluate venous reflux in the spermatic cord. Valsalva-induced reflux occurred on the left side in 83% and on the right side in 59% of 118 patients without clinical varicoceles and there was no difference in incidence between fertile and infertile men. The significance of Valsalva-induced reflux should be questioned. Greater importance should be attributed to the spontaneous venous reflux that occurred during quiet respiration in the majority of patients with varicoceles. Seven velocity waveform patterns are described and these are thought to represent increasing degrees of internal spermatic vein reflux and provide a basis on which it is possible to grade varicoceles. The Doppler grades correlated with the size of the varicocele, and with the internal spermatic vein diameter and testosterone concentrations.     

Increase of decorin content in articular cartilage following running

The effect of long distance running exercise (40 km/day for 15 weeks, five days a week) on the decorin content of articular cartilage from the knee joint was studied in female beagle dogs. Samples from load bearing sites on the lateral plateau of the tibia (TL), and pooled material from two minimum load bearing sites on the posterior section of lateral (FLP) and medial (FMP) femoral condyles were analyzed. The running exercise protocol did not lead to significant changes in the overall glycosaminoglycan content of the cartilage. However, the amount of decorin significantly increased in the TL samples, and also in the FMP pool. These results support earlier in vitro observations that decorin synthesis is stimulated by loading, independent of the synthesis of aggrecan.     

The effect of triple pelvic osteotomy on the articular contact area of the hip joint in dysplastic dogs: an in vitro experimental study

This study compares the frequency of signs and symptoms from the cervical spine in 24 patients diagnosed with Meniere's disease and 24 control subjects from a population sample. From a previous controlled comparative study concerning signs and symptoms of craniomandibular disorders, 24 patients diagnosed with Meniere's disease (10 males and 14 females) and their 24 matched control subjects participated in this investigation on the state of the cervical spine. Symptoms of cervical spine disorders, such as head and neck/shoulder pain, were all significantly more frequent in the patient group than in the control group. Most of the patients (75%) reported a strong association between head neck movements in the atlanto-occipital and atlanto-axial joints and triggered attacks of vertigo. Also, 29% of the patients could influence their tinnitus by mandibular movements. Signs of cervical spine disorders, such as limitations in side-bending and rotation movements, were significantly more frequent in the patient group than in the control group. Tenderness to palpation of the transverse processes of the atlas and the axis, the upper and middle trapezius, and the levator scapulae muscle were also significantly more frequent in the patient group. The study shows a much higher prevalence of signs and symptoms of cervical spine disorders in patients diagnosed with Meniere's disease compared with control subjects from the general population.     

Low-selenium diet, bone, and articular cartilage in rats

The pathophysiology of secondary osteoarthritis remains largely obscure. Our attention has been drawn to Kashin-Beck disease (KBD), which has been attributed to Se deficiency. To obtain information regarding the prevention, prediction of progression, and treatment of this condition, we performed histological and biochemical studies on bone and articular cartilage specimens obtained from rats fed a low-Se diet. A low-Se diet was prepared and fed to Wistar rats for 3-11 mo, after which the rats were killed under general anesthesia, and their articular cartilages were studied microscopically and electron microscopically. The bone mineral density (BMD) of the femur was determined by the microdensitometry method and ash weight. In addition, serum Se, Ca, P, Alk Phos, T3, T4, and urinary Se were measured. In the low-Se group, impaired weight gain was observed from the 5th mo, and head alopecia was found in 60% of the animals. Microscopically, no clear changes in the articular chondrocytes were apparent, whereas with the electron microscope, chondrocytes in the deep layer showed degeneration of nuclei and endoplasmic reticular ballooning. From the 5th mo, a decrease in BMD (ash weight) was noted. Serum Se concentrations, alkaline phosphatase activity, and urine Se concentrations were decreased in the Se-deficient rats, whereas serum Ca, P, T3, and T4 values did not differ from those of a control group. Also, a decrease in sulfotransferase activity, which is involved in transfer in the process of synthesis of glycosaminoglycan, which is a proteoglycan carbohydrate chain, was found.(ABSTRACT TRUNCATED AT 250 WORDS)     

Experimental evaluation of theoretical contact forces in the cat patellofemoral joint

The purpose of this study was to evaluate the accuracy of patellofemoral contact forces predicted from a planar model of the patella by comparison with experimentally determined in situ contact forces. Patellofemoral contact pressures and areas were measured experimentally in an animal preparation with pressure sensitive film. Patellar tendon forces and lines of action used as input to the model were measured in the intact joint of the same preparation. Predicted and measured contact forces at different joint loads were compared at three different joint angles using linear regression analysis. r2-coefficients ranged from 0.94 to 0.95, and the slopes of the regression lines ranged from 1.64 to 2.11 for the three joint angles. The high r2-coefficients for all comparisons indicate that both methods were able to quantify the relative changes in the cat patellofemoral contact forces under different loading conditions accurately. However, the consistent finding of slopes greater than 1.0 indicates that the measured contact forces were systematically larger than the corresponding predicted forces. Analysis of the possible sources for the observed discrepancies between predicted and measured contact forces suggested that the directly measured patellar tendon forces were the most likely candidate causing the systematic differences. The results of this study suggest that a relatively simple model of the patellofemoral joint appears to be valid to quantify joint contact forces if appropriate patellar tendon force values can be provided as input to the model.