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PubMed1980

Differential changes in cartilage cell proliferation and cell density in the rat craniofacial complex during secondary palate development.

During mammalian secondary palate formation sagittal growth of the lower face has been shown to be more rapid than that of the upper face, and the tongue and mandible extend beneath the primary palate. In order to identify factors contributing to this differential growth pattern, cellular and morphologic growth of the major cartilages of the upper and lower facial regions were studied in radioautographic sections labeled with tritiated thymidine. Evaluation of cell-density recordings, labeling indices, and structural dimensions revealed significant differences between Meckel's cartilage in the lower face, and the nasal cartilage and anterior cranial base cartilage in the upper face. After formation of the precartilaginous blastema, labeling indices were high in Meckel's cartilage (20-30%), but very low in the nasal cartilage and the anterior cranial base (0-2%). During secondary palate formation the volume of Meckel's cartilage increased more rapidly than the other cartilages and its growth was primarily in the sagittal direction. Between days 15 and 17, the increase in the length of Meckel's cartilage (165%) was approximately twice as great as the increase in the combined length of the nasal cartilage and the anterior cranial base (77%). During this period induction of cleft palate with some teratogens has been shown to severely retard growth of Meckel's cartilage and produce mandibular retrognathia that contributes to delayed elevation of the palatal shelves. Therefore, extensive cell proliferation in Meckel's cartilage, during a period of limited proliferation in other craniofacial cartilages, appears to contribute to its rapid growth and its differential sensitivity to growth inhibition.

Animals↗
PubMed2002

Risk factors for progressive cartilage loss in the knee: a longitudinal magnetic resonance imaging study in forty-three patients.

OBJECTIVE: To evaluate the rate of progression of cartilage loss in the knee joint using magnetic resonance imaging (MRI) and to evaluate potential risk factors for more rapid cartilage loss. METHODS: We evaluated baseline and followup MRIs of the knees in 43 patients (minimum time interval of 1 year, mean 1.8 years, range 52-285 weeks). Cartilage loss was graded in the anterior, central, and posterior regions of the medial and lateral knee compartments. Knee joints were also evaluated for other pathology. Data were analyzed using analysis of variance models. RESULTS: Patients who had sustained meniscal tears showed a higher average rate of progression of cartilage loss (22%) than that seen in those who had intact menisci (14.9%) (P <or= 0.018). Anterior cruciate ligament (ACL) tears had a borderline significant influence (P <or= 0.06) on the progression of cartilage pathology. Lesions located in the central region of the medial compartment were more likely to progress to more advanced cartilage pathology (progression rate 28%; P <or= 0.003) than lesions in the anterior (19%; P <or= 0.564) and posterior (17%; P <or= 0.957) regions or lesions located in the lateral compartment (average progression rate 15%; P <or= 0.707). Lesions located in the anterior region of the lateral compartment showed less progression of cartilage degradation (6%; P <or= 0.001). No specific grade of lesion identified at baseline had a predilection for more rapid cartilage loss (P <or= 0.93). CONCLUSION: MRI can detect interval cartilage loss in patients over a short period (<2 years). The presence of meniscal and ACL tears was associated with more rapid cartilage loss. Cartilage lesions located in the central region of the medial compartment showed more rapid progression of cartilage loss than cartilage lesions in the anterior and posterior portions of the medial compartment. The findings in this study suggest that patients entering clinical trials investigating antiarthritis regimens may need to be randomized based on location of the lesion.

Adolescent↗
PubMed2003

The pathobiology of focal lesion development in aging human articular cartilage and molecular matrix changes characteristic of osteoarthritis.

OBJECTIVE: To determine if early focal lesions seen in aging exhibit molecular changes in the extracellular matrix that are similar to those seen in osteoarthritis (OA) and to examine the interrelationships between matrix degradation and synthesis and how they relate to cartilage turnover. METHODS: Condylar cartilage was obtained postmortem from lesion-free joints and from the lesion (where present as well as) from areas adjacent to and remote from the lesion of 31 knees without signs of joint injury (damage to ligaments or menisci). Cartilage was graded histologically and assayed for type II collagen and proteoglycan aggrecan glycosaminoglycan (GAG) contents and turnover (specifically, type II collagen denaturation and its cleavage by collagenase), type II collagen synthesis (C-propeptide [CPII] content), and aggrecan turnover (846 epitope content). To study the degradation of aggrecan reflected by the release of GAG, we cultured cartilage samples from 10 knees. RESULTS: The more degenerated cartilage from the lesion and adjacent area exhibited significantly more collagen cleavage by collagenase than did cartilage remote from the lesion. Type II collagen denaturation and synthesis were also significantly elevated in the lesion and adjacent cartilage, but neither cleavage nor denaturation correlated with synthesis. Type II collagen content decreased with increasing degeneration, with the lowest levels present in the lesion. Collagen content was indirectly related to denaturation and cleavage adjacent to and remote from the lesion and to denaturation within the lesion. Collagen cleavage and denaturation adjacent to and remote from the lesion were directly interrelated. Cartilage from the lesion contained significantly less GAG than did cartilage adjacent to and remote from the lesion. Aggrecan turnover (846 epitope) was also elevated in both the lesion and adjacent cartilage, whereas GAG release was elevated only in the lesion. GAG and 846 epitope contents were interrelated only at sites remote from the lesion. There was also a direct correlation between collagen and GAG contents in the lesion and in adjacent sites. This correlation was also seen between collagen synthesis (CPII) and the 846 epitope. CONCLUSION: These results demonstrate that lesions seen in aging exhibit molecular changes in matrix turnover similar to those seen in OA articular cartilage at arthroplasty, but not in healthy normal aging cartilage. The direct relationships between type II collagen cleavage and denaturation and the inverse relationship between type II collagen content and cleavage or denaturation implicate collagenase activity and damage to collagen in this loss of collagen during lesion development. The lack of correlation of the increased synthesis with the degradation or content of type II collagen indicates that these aspects of turnover are not coordinated in the pathologic state. However, the direct relationship between collagen and GAG contents in and adjacent to the lesion illustrates the structural interrelationships of collagen and proteoglycan aggrecan molecules. These results suggest that these focal lesions represent the development of early OA and that this involves the progressive damage to articular cartilage surrounding the lesion as part of the process of the development of idiopathic OA.

Adult↗
PubMed2004

Identification of mesenchymal progenitor cells in normal and osteoarthritic human articular cartilage.

OBJECTIVE: To determine the presence of mesenchymal progenitor cells (MPCs) in human articular cartilage. METHODS: Primary cell cultures established from normal and osteoarthritic (OA) human knee articular cartilage were analyzed for the expression of CD105 and CD166, cell surface markers whose coexpression defines mesenchymal stem cells (MSCs) in bone marrow and perichondrium. The potential of cartilage cells to differentiate to adipogenic, osteogenic, and chondrogenic lineages was analyzed after immunomagnetic selection for CD105+/CD166+ cells and was compared with bone marrow-derived MSCs (BM-MSCs). RESULTS: Up to 95% of isolated cartilage cells were CD105+ and approximately 5% were CD166+. The mean +/- SEM percentage of CD105+/CD166+ cells in normal cartilage was 3.49 +/- 1.93%. Primary cell cultures from OA cartilage contained significantly increased numbers of CD105+/CD166+ cells. Confocal microscopy confirmed the coexpression of both markers in the majority of BM-MSCs and a subpopulation of cartilage cells. Differentiation to adipocytes occurred in cartilage-derived cell cultures, as indicated by characteristic cell morphology and oil red O staining of lipid vacuoles. Osteogenesis was observed in isolated CD105+/CD166+ cells as well as in primary chondrocytes cultured in the presence of osteogenic supplements. Purified cartilage-derived CD105+/CD166+ cells did not express markers of differentiated chondrocytes. However, the cells were capable of chondrocytic differentiation and formed cartilage tissue in micromass pellet cultures. CONCLUSION: These findings indicate that multipotential MPCs are present in adult human articular cartilage and that their frequency is increased in OA cartilage. This observation has implications for understanding the intrinsic repair capacity of articular cartilage and raises the possibility that these progenitor cells might be involved in the pathogenesis of arthritis.

Activated-Leukocyte Cell Adhesion Molecule↗
PubMed2004

Age dependency of cartilage magnetic resonance imaging T2 relaxation times in asymptomatic women.

OBJECTIVE: Because the magnetic resonance imaging (MRI) transverse relaxation time (T2) of cartilage is sensitive to organization of collagen fibers in the cartilage, it may be a noninvasive image marker for senescent changes in cartilage collagen and early cartilage degeneration. The purpose of this study was to determine age-dependent differences in cartilage T2 values in healthy asymptomatic women. METHODS: Quantitative T2 maps of patellar cartilage from 30 asymptomatic women ages 22-86 years were obtained using a 3.0T MRI scanner. The study population was stratified by age into 4 cohorts: 18-30, 31-45, 46-65, and 66-86 years. Spatial differences in cartilage T2 were determined as a function of normalized distance from bone. Older groups were compared with the 18-30-year-old group to determine the effects of age on cartilage T2 values. Regions were considered statistically significantly different if the mean T2 values between groups differed at P < 0.05. RESULTS: Mean cartilage T2 profiles were nearly identical for the 2 youngest cohorts. Compared with the 18-30-year-old group, T2 values were statistically significantly longer in the superficial 40% of cartilage in the 46-65-year-old group and over the entire cartilage thickness in the 66-86-year-old group. CONCLUSION: The location of T2 elevations in women over the age of 45 years is consistent with the theory that senescent changes of cartilage collagen begin near the articular surface and progress to the deeper cartilage with advancing age.

Adolescent↗
PubMed2005

The relationship between body composition and knee cartilage volume in healthy, middle-aged subjects.

OBJECTIVE: Although obesity is widely accepted as a risk factor for knee osteoarthritis, it is not clear whether individual components of body composition, such as the mass and distribution of muscle and fat, are associated with development of the disease. This study examined the effect of measures of body composition on the longitudinal change in tibial cartilage volume. METHODS: Body composition, assessed via dual x-ray absorptiometry, and tibial cartilage volume, assessed via magnetic resonance imaging, were measured in 86 healthy men and women who were mid-life in age. Change in tibial cartilage volume was assessed by imaging each knee 2 years after the baseline measurement and determining the difference from baseline in tibial cartilage volume. Correlations were determined between the muscle and fat mass of the arm, leg, and total body and the volume of the lateral- and medial-tibial cartilage, as well as the change in tibial cartilage volume over 2 years, after adjusting for confounders. RESULTS: There was a significant association between muscle mass and the medial-tibial cartilage volume, independent of age, sex, body mass index, tibial bone area, and level of physical activity. Although there was a positive association between muscle mass and the lateral-tibial cartilage volume, this did not persist after adjustment for confounders. Loss of muscle mass was associated with an increased loss of medial- and lateral-tibial cartilage over 2 years, after adjusting for confounders. No relationship was apparent between fat mass and either medial- or lateral-tibial cartilage volume, or between fat mass and change in either medial- or lateral-tibial cartilage volume over 2 years, after adjusting for confounders. CONCLUSION: Muscle mass is an independent predictor of medial-tibial cartilage volume in healthy people in mid-life and is associated with a reduction in the rate of loss of tibial cartilage. This suggests that increased muscle mass may be protective against the onset of osteoarthritis.

Absorptiometry, Photon↗
PubMed2005

Tonic activation of hypoxia-inducible factor 1alpha in avascular articular cartilage and implications for metabolic homeostasis.

OBJECTIVE: To determine whether oxygen-dependent activation patterns of hypoxia-inducible factor 1alpha (HIF-1alpha) observed in vascularized tissues are conserved within avascular and hypoxic articular cartilage and whether HIF-1alpha affects cartilage matrix synthesis. METHODS: Explants of bovine articular cartilage and primary chondrocytes were exposed to normoxia (21% O2), hypoxia (2% O2), and simulated hypoxia (21% O2 plus CoCl2). Western blot and immunofluorescence analyses of HIF-1alpha were performed to determine HIF-1alpha activation patterns. To simulate cartilage loss from disease or injury, the top layers of cartilage were removed from osteochondral explants, and the residual cartilage was assessed for HIF-1alpha immunolocalization and proteoglycan synthesis. RESULTS: We demonstrated continuous nuclear translocation of HIF-1alpha in deeper layers of intact articular cartilage. HIF-1alpha was not completely degraded in chondrocytes exposed to normoxia, but rather, colocalized to the Golgi complex, a finding not previously reported for any cell type. Following alteration of the oxygen gradient by removal of the top layers of cartilage, predominantly perinuclear HIF-1alpha was found in the deeper layers. Restoration of intranuclear HIF-1alpha to these areas was achieved by hypoxia and simulated hypoxia. Under conditions in which HIF-1alpha was inactivated, matrix synthetic activity was altered (P < 0.0001) compared with control cartilage. CONCLUSION: These findings demonstrate that hypoxia-dependent activation of HIF-1alpha is highly conserved and that changes in oxygen tensions following cartilage loss from injury or disease alter cartilage metabolism in part by changing HIF-1alpha activity. The discovery of tonic activation of HIF-1alpha within intact articular cartilage underscores its potential importance to cartilage homeostasis.

Animals↗
PubMed1999

Hyaluronan suppresses fibronectin fragment-mediated damage to human cartilage explant cultures by enhancing proteoglycan synthesis.

Hyaluronic acid, recently renamed hyaluronan, has been used as a therapeutic intervention in the treatment of osteoarthritis. We have reported that high-molecular-weight (800 kDa) hyaluronan is effective in blocking the catabolic action of fibronectin fragments in explant cultures of bovine cartilage and in an experimental in vivo model of damage to the rabbit knee joint. The fibronectin fragments induce catabolic cytokines in human cartilage, which, in turn, suppress proteoglycan synthesis and induce matrix metalloproteinases to decrease the proteoglycan content. Since the clinical target of high-molecular-weight hyaluronan is human cartilage, which may differ in certain ways from bovine cartilage, we tested the effect on human knee cartilage. We found that 1 mg/ml hyaluronan completely blocked fibronectin fragment-mediated decreases in proteoglycan content in five of five specimens of cartilage from the human knee. This was associated with binding of exogenous hyaluronan to the superficial surface, suppressed penetration of the fibronectin fragment into the cartilage, decreased expression for the first week in culture of one of the matrix metalloproteinases involved in cartilage degradation, matrix metalloproteinase-3, and proteoglycan synthesis rates that increased to supernormal levels. However, the appearance of the NITEGE and VDIPEN neoepitopes, indices of cartilage degradation, was not blocked but was delayed by 1 week. The addition of hyaluronan to cartilage previously damaged by the fibronectin fragments or to osteoarthritic cartilage fully restored the proteoglycan content to control levels. We conclude that hyaluronan blocked damage at least partly by blocking penetration of the fibronectin fragments and slowing matrix metalloproteinase expression. However, the major effect on blocking damage and promoting repair may be through enhanced proteoglycan synthesis, a mechanism that requires further study. Nonetheless, these data clearly demonstrate that hyaluronan completely protected human cartilage in explant culture and facilitated a full restoration of proteoglycan in damaged cartilage.

Adolescent↗
PubMed1984

Hormonal stimulation of avian embryonic cartilage growth in vitro: histologic and ultrastructural features.

We studied the histologic and ultrastructural features of embryonic chick cartilage after the cartilage had been incubated in serum-free medium that contained hormones and growth factors known to stimulate in vitro cartilage growth. Pelvic cartilages from 9 d chick embryos were incubated in BGJb ( Fitton -Jackson modification) medium alone (control) or medium containing one of the following: N6 monobutyryl cyclic AMP 0.5 mM, forskolin 100 microM, triiodothyronine (T3) 10 nM, insulin 45 nM, or somatomedin C 0.67 nM. At the end of 3 d of incubation the cartilages were fixed in buffered formalin. Significant growth (increases in size, wet and dry weight) was seen with each treatment group. N6-Monobutyryl cAMP treated cartilage had an increased number of flattened immature chondrocytes with large nuclei and prominent nucleoli. The histologic and ultrastructural features of forskolin treated cartilage were indistinguishable from N6-monobutyryl cAMP treatment. The T3 treated cartilage contained large hypertrophic chondrocytes with prominent lacunar typical of mature cartilage. T3 treated cartilage had considerable vacuole formation and dilated endoplasmic reticulum. Insulin and somatomedin treated cartilage had histologic appearance similar to control cartilage. Thus, the effects of various hormones on embryonic cartilage growth in vitro can be separated as to whether growth is the result of chondrocytic hyperplasia (cyclic AMP mediated), chondrocytic hypertrophy with maturation (T3), or a combination of both hyperplasia and hypertrophy (insulin and somatomedin-C).

Animals↗
PubMed2000

Rapid degradation of articular cartilage proteoglycan by neutrophils: comparison with macrophages and synovial fibroblasts.

OBJECTIVE AND DESIGN: To determine and compare the proteoglycan degradative properties of neutrophils, macrophages and synoviocytes in cultures of articular cartilage. MATERIAL OF SUBJECTS: Bovine articular cartilage was aseptically isolated from metacarpopharyngeal joints. Neutrophils and macrophages were isolated from normal human blood and bovine synovial fibroblasts were isolated from explant cultures before being incubated with the cartilage. TREATMENT: Neutrophils, macrophages or synovial fibroblasts (1 x 10(6)-8 x 10(6)) were incubated with 35SO4 labelled cartilage for 2.5-72 h. METHODS: Cartilage degradation was measured as a loss of 35SO4 into the cartilage medium as a percentage of the total labelled proteoglycan in the cartilage slice. Statistical significances were determined using a 2-tailed unpaired Student's t-test. RESULTS: Neutrophils rapidly degraded articular cartilage. After 2.5 hours of culture, neutrophils degraded cartilage proteoglycan up to 28 times more than either macrophages or synovial fibroblasts. CONCLUSIONS: Neutrophils induce rapid damage to articular cartilage proteoglycan, whereas in comparison, macrophages and synovial fibroblasts degrade articular cartilage proteoglycans poorly. These findings indicate that at least under conditions where the influence of cellular-cellular interactions and soluble mediator action are excluded, adhesion of neutrophils to articular cartilage is sufficient to stimulate rapid and marked cartilage degradation compared to the other two cell types.

Animals↗
PubMed2006

Abnormal expression of Col X, PTHrP, TGF-beta, bFGF, and VEGF in cartilage with Kashin-Beck disease.

The purpose of the current study was to investigate the abnormal expression of Col X, PTHrP, TGF-beta, bFGF, and VEGF in cartilage from patients with Kashin-Beck disease (KBD) to understand the pathogenesis of chondronecrosis in KBD. Articular cartilage and growth plate cartilage collected were divided into four groups: control children (8 samples, 5 cases), KBD children (19 samples, 9 cases), control adults (8 samples, 6 cases), and KBD adults (16 samples, 15 cases). The presence of PTHrP, TGF-beta1, bFGF, VEGF, and collagen X in articular cartilage and in growth plate cartilage was analyzed by immunohistochemistry. Articular cartilage and growth plate were each divided in three zones, and the rate of positive cells was counted by light microscope for cytoplasmic and pericellular staining. Results showed that (1) in KBD children, Col X expression was lower in the deep zone of growth plate cartilage than in normal children; in articular cartilage of KBD adults, however, collagen X expression was higher in the middle zone compared to the controls; (2) staining for bFGF, PTHrP, TGF-beta1, and VEGF in KBD adult patients was prominent in the chondrocyte clusters and the eroded surface of articular cartilage, and the percentage of chondrocyte staining was significantly higher than in control samples (t = 3.64-10.34, df = 12 for children and 19 for adults, P = 0.002-0.0001); and (3) the enhanced PTHrP, TGF-beta1, and VEGF staining in the deep and middle zone of KBD articular cartilage correlated with the high incidence of chondronecrosis in the middle zone (48.5% +/- 10.2%) and deep zone (70.6% +/- 27.0%) of adult KBD cartilage. In conclusion, Col X expression was reduced in areas of chondrocyte necrosis in the deep zone of KBD articular cartilage, indicating changes in terminal chondrocyte differentiation. PTHrP, TGF-beta1, and VEGF expression was significantly altered and indicated degenerative changes in KBD cartilage, which initially resemble those occurring in osteoarthritis, but lead eventually to chondronecrosis, an event not observed in osteoarthritis.

Adult↗
PubMed1996

Modeling axi-symmetrical joint contact with biphasic cartilage layers--an asymptotic solution.

The articular contact surfaces in human and animal joints are highly variable. Articular cartilage thickness and the material properties of the cartilage vary as a function of location in the joint and may also change in the pathologic state. In order to study practical joint contact problems, we extended the model for the contact of two biphasic cartilage layers proposed by Ateshian et al. [J. Biomechanics 27, 1347-1360 (1994)] by combining the assumption of the kinetic relationship from classical contact mechanics with the joint contact model for biphasic articular cartilage. In order to illustrate the characteristics of the proposed model, the contact problem was solved numerically for different curvatures of the contact surfaces, and for different thicknesses and material properties of the cartilage layers. Each cartilage layer was assumed to have constant thickness within the contact region. The contact radius, the relative displacement between the contacting bodies, contact pressure, and the stress distributions within the cartilage layers were calculated by applying a step load for a time period of 200 s. The contact radius was found to be sensitive to the change in thickness of the cartilage, and was not very sensitive to the change in the material property of the cartilage. The peak effective stress and the maximal shear stress were predicted to occur at the cartilage-bone interface for all simulated cases, which is in agreement with other theoretical research and supports the experimental findings in the literature on the origins of cartilage damage. For articular cartilage layers of different thicknesses, the stresses in the thick layer were found to be higher than those in the thin layer. Compared to other models of joint contact, the present model offers more possibilities for investigating practical applications, such as simulating the effects associated with cartilage degeneration in diseases such as osteoarthritis, and comparing theoretical predictions with experimental measurements of pressure distribution and contact area in joints.

Cartilage, Articular↗
PubMed1985

Phosphotyrosine and phosphoprotein phosphatase activity of alkaline phosphatase in mineralizing cartilage.

We used embryonic skeletal cartilage known to have high levels of alkaline phosphatase activity to determine whether growing cartilage has phosphotyrosine phosphatase activity and phosphotyrosinyl histone phosphatase activity at physiologic pH. Embryonic chick pelvic cartilage and fetal pig scapular growth-plate cartilage were assayed using phosphotyrosine as substrate at pH 7.5 and the amount of tyrosine generated measured. Both cartilage models had Km for phosphotyrosine between 6 to 24 mus mol/L. Phosphotyrosine phosphatase activity correlated with alkaline phosphatase activity as assessed by (1) distribution of histologic staining for alkaline phosphatase within the cartilages, (2) hormonal stimulation of cartilage alkaline phosphatase activity in vitro, (3) comparison of alkaline phosphatase and phosphotyrosine phosphatase activities in the presence of known inhibitors (vanadate, levamisole, homoarginine, and zinc), and (4) assaying chick epiphyseal cartilage alkaline phosphatase purified to homogeneity for phosphotyrosine phosphatase activity. Areas of cartilage with elevated alkaline phosphatase activity also had raised phosphotyrosine phosphatase activity. Triiodothyronine, a known stimulator of cartilage alkaline phosphatase, increased chick cartilage alkaline phosphatase activity 88% and phosphotyrosine phosphatase activity 106%, and stimulated porcine growth-plate cartilage alkaline phosphatase activity 91% and phosphotyrosine phosphatase activity 145% after 3 days of in vitro incubation. Each of the inhibitors block alkaline phosphatase and phosphotyrosine phosphatase activities. The purified alkaline phosphatase had a Km for phosphotyrosine of 18 mus mol/L and Vmax of 5700 nmol tyrosine/mg protein/h, which is well over 1000-fold higher than the phosphotyrosine phosphatase activity found in the above preparations of pelvic and scapular cartilage.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗
PubMed1989

Articular cartilage lesions of the knee.

The pathogenesis and clinical significance of articular cartilage lesions of the knee persist as topics of considerable interest among orthopedic surgeons. This study was designed to assess the association of articular cartilage degeneration with concomitant intraarticular abnormalities and to correlate the prevalence and severity of articular cartilage damage with preoperative historical and physical exam findings in patients presenting with knee pain. Twenty-six history and physical exam data points were prospectively collected from 192 patients (200 knees), consecutively undergoing arthroscopic knee surgery. During surgery, all articular cartilage lesions were recorded with respect to size, location, and character and were graded according to Oglivie-Harris et al. All concomitant knee joint abnormalities were simultaneously recorded. Of 200 knees examined arthroscopically, 12 knees revealed no demonstrable etiology for the presenting symptoms, 65 knees revealed assorted intraarticular pathology but no articular cartilage degeneration, and the remaining 123 knees revealed a total of 211 articular cartilage lesions (103 femoral, 72 patellar, 36 tibial); 7 femoral, 6 patellar and 0 tibial lesions were completely isolated (no concomitant knee joint pathology). The concomitance of femoral defects with tibial lesions was highly significant (p = 0.01). Femoral and tibial articular cartilage lesions were strikingly correlated with the presence of an unstable torn meniscus (p less than 0.001). Medial compartment articular cartilage lesions were significantly more common (p = 0.001), more closely associated with meniscal derangement, and appreciably more severe than lateral compartment lesions. In 75% of anterior cruciate ligament-deficient knees with concomitant articular cartilage degeneration, the duration from injury to surgery was greater than 9 months, and in each of these cases, a history of reinjury to the knee was elicited. From these data one can conclude that: (a) in some patients with painful knees, isolated articular cartilage lesions may be the only abnormality noted at arthroscopy; (b) unstable meniscal tears are significantly associated with destruction of articular cartilage; (c) the medial compartment is particularly susceptible to articular cartilage degeneration; and (d) in our series, anterior cruciate ligament tears were increasingly associated with articular cartilage destruction as the elapsed time from injury to arthroscopy increased.

Adult↗
PubMed1990

Endochondral mineralization in cartilage organoid culture.

In the development of secondary bone, mineralization of the cartilage matrix is the first step in endochondral mineralization. The circumstances of cartilage mineralization are not known. Influences of the periosteal tissue have been mentioned. In order to investigate the role of osteoblastic cells in endochondral mineralization, cartilage organoid cultures were induced to mineralize by the addition of beta-glycerophosphate (beta-GP). In cartilage organoid culture, embryonic mouse limb bud mesenchymal cells were grown at high-density. The cells differentiated into mature chondrocytes and produced hyaline cartilage matrix. When cartilage had formed after 6 days in vitro, 10 mM beta-GP was added. The developed mineralized cartilage was investigated by morphological means. Seven days after the addition of beta-GP, the first mineralized spots were visible mainly in the internodular, noncartilage tissue. After 12 to 14 days, large areas of cartilage were mineralized, and after 21 days, nearly the whole culture had been mineralized. Electron microscopic investigations showed a dramatic alteration of the cartilage matrix followed by a homogeneous mineralization of the cartilage matrix. The chondrocytes in the mineralized area died and faded. Typical rod-like apatite crystals were visible at the border between the mineralized and the unmineralized matrix. This result closely resembles the in vivo situation of cartilage mineralization. Addition of osteoblastic calvarial cells enhanced the mineralization process, as did the addition of conditioned medium of calvarial cell monolayers. Under these treatments, mineralization started after 3 days and reached a maximum after 14 days. On the other hand, addition of mouse skin fibroblast-like cells without a direct contact to the cartilage inhibited cartilage mineralization. These results indicate that osteoblastic cells induce endochondral mineralization, whereas fibroblast-like cells inhibit this mineralization via soluble factors.

Animals↗
PubMed2005

Contrasting alterations of apposed and unapposed articular cartilage during joint contracture formation.

OBJECTIVE: To quantify histologic articular cartilage alterations after immobilization, distinguishing between apposed and unapposed sites in an animal model of joint contracture. DESIGN: Experimental controlled trial. SETTING: Laboratory, in vivo study. ANIMALS: Adult male Sprague-Dawley rats (N=128). INTERVENTIONS: One hundred seventeen animals had 1 knee internally immobilized or sham-operated for 2, 4, 8, 16, or 32 weeks. One knee in 11 nonoperated animals served as controls. Main outcome measures On standardized sections, we identified femur and tibia cartilage sites that were apposed or that were unapposed. We quantified 4 characteristics: number of chondrocytes in the superficial and deep cartilage; matrix staining intensity to toluidine blue; surface irregularity of articular cartilage; and thickness of cartilage. RESULTS: Immobilized knees harbored fewer chondrocytes in the superficial cartilage at apposed sites and in the deep cartilage at unapposed sites. Matrix staining decreased only at unapposed sites. Cartilage surface became significantly more irregular at both sites but cartilage thickness remained unchanged. Noncartilaginous tissues appeared only at unapposed sites in the superficial and deep cartilage. CONCLUSIONS: Immobilization led to contrasting patterns of cartilage degeneration at apposed sites compared with unapposed sites. These results suggest distinct pathogenetic pathways for cartilage alterations, possibly through absence of mechanical forces (negative mechanotransduction) at unapposed sites and cyclic pressure at apposed sites. Considering the limited potential for cartilage self-repair, these results support the need for early diagnosis and aggressive mobilization of joints that are developing contractures.

Animals↗
PubMed2006

Fourier transform infrared imaging spectroscopy investigations in the pathogenesis and repair of cartilage.

Significant complications in the management of osteoarthritis (OA) are the inability to identify early cartilage changes during the development of the disease, and the lack of techniques to evaluate the tissue response to therapeutic and tissue engineering interventions. In recent studies several spectroscopic parameters have been elucidated by Fourier transform infrared imaging spectroscopy (FT-IRIS) that enable evaluation of molecular and compositional changes in human cartilage with progressively severe OA, and in repair cartilage from animal models. FT-IRIS permits evaluation of early-stage matrix changes in the primary components of cartilage, collagen and proteoglycan on histological sections at a spatial resolution of approximately 6.25 microm. In osteoarthritic cartilage, the collagen integrity, monitored by the ratio of peak areas at 1338 cm(-1)/Amide II, was found to correspond to the histological Mankin grade, the gold standard scale utilized to evaluate cartilage degeneration. Apparent matrix degradation was observable in the deep zone of cartilage even in the early stages of OA. FT-IRIS studies also found that within the territorial matrix of the cartilage cells (chondrocytes), proteoglycan content increased with progression of cartilage degeneration while the collagen content remained the same, but the collagen integrity decreased. Regenerative (repair) tissue from microfracture treatment of an equine cartilage defect showed significant changes in collagen distribution and loss in proteoglycan content compared to the adjacent normal cartilage, with collagen fibrils demonstrating a random orientation in most of the repair tissue. These studies demonstrate that FT-IRIS is a powerful technique that can provide detailed ultrastructural information on heterogeneous tissues such as diseased cartilage and thus has great potential as a diagnostic modality for cartilage degradation and repair.

Aged↗
PubMed2004

Testican-1, an inhibitor of pro-MMP-2 activation, is expressed in cartilage.

OBJECTIVE: Recently, testican-1 has been described to be an inhibitor of MT1-MMP and MT3-MMP mediated pro-MMP-2 activation. As MT1-MMP mediated pro-MMP-2 activation is of significance for cartilage destruction in osteoarthritis, we studied the expression and localization of testican-1 in human articular cartilage. METHODS: Cartilage samples from the medial and lateral tibia plateau were obtained from osteoarthritic patients who underwent joint replacements, and were graded histomorphologically by Mankin score. Testican-1 expression was assessed in RNA isolated directly from cartilage as well as in freshly isolated chondrocytes by reverse transcriptase-polymerase chain reaction (RT-PCR) and quantified by real-time RT-PCR. Testican-1 protein was localized by immunohistochemistry in human osteoarthritic cartilage samples, in human fetal knee joint, and in knees from mice. RESULTS: Testican-1 mRNA could be detected in cartilage and in freshly isolated chondrocytes both from moderately and from severely damaged osteoarthritic cartilage. In the same donor, expression in chondrocytes from more severely affected regions was decreased compared with chondrocytes from less affected regions. By immunolocalization, testican-1 protein could be detected in chondrocytes predominantly of the superficial and transitional zones. Matrix staining in these zones was greatly reduced in samples from more severely affected osteoarthritic cartilage. A similar distribution was found in the articular cartilage of knees from 7-week-old mice. In addition to articular cartilage, testican-1 was also present in growth plate cartilage. CONCLUSIONS: Testican-1 is a component of cartilage, both of the joint and of the growth plate. Given its activity as an inhibitor of MT1-MMP mediated pro-MMP-2 activation, it is reasonable to speculate that it participates in the regulation of matrix turnover in cartilage.

Aged↗