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PubMed1981

Regulation of tumor invasion by cartilage-derived anti-invasion factor in vitro.

The resistance of cartilage to tumor invasion was studied with the use of a novel in vitro culture system. Articular cartilage obtained from fresh metacarpophalangeal joints of preadolescent bovines was used as a growth surface for human TE-85 osteosarcoma cells and foreskin fibroblasts. Cartilage disks formed the bottoms of stainless-steel cylinders, providing closed growth chambers for these cells. Both invasive osteosarcoma cells and normal fibroblasts were unable to penetrate viable, unextracted cartilage during a 2-week culture period. When cartilage was devitalized by freezing and thawing, the tissue remained resistant to invasion. Cartilage, extracted with either 1 or 3 M guanidine hydrochloride, was invaded by osteosarcoma cells, but not by control fibroblasts. Invasion by osteosarcoma cells into salt-extracted cartilage was abolished when low concentrations of a cartilage-derived, anti-invasion factor were added to the culture medium. These data provided evidence that the resistance of cartilage to tumor invasion is regulated in part by tissue-derived proteinase inhibitors.

Cartilage↗
PubMed1982

Influence of cartilage particle size and proteoglycan aggregation on immobilization of proteoglycans.

Mechanisms by which proteoglycan aggregates are retained within cartilage were studied using two approaches: mechanical fragmentation of cartilage and reassociation of proteoglycans within extracted cartilage. The extractability of proteoglycans from fresh bovine nasal cartilage with low ionic strength buffer was found to vary from 13 to 45% depending upon the degree of cartilage fragmentation. Forty per cent of those extracted from finely fragmented cartilage (5-20-mu diameter) were found to be in aggregates which contained "link" proteins. A method was developed to reintroduce proteoglycans, which had been extracted with guanidine hydrochloride, into cartilage from which they had been extracted. Stability of the newly formed associations was assessed by re-extraction with a guanidine hydrochloride gradient. Purified proteoglycans alone or reduced and alkylated proteoglycans formed associations which were disrupted with less than 2 M guanidine hydrochloride. Addition of "link" proteins resulted in associations which required 2-4 M guanidine hydrochloride to be re-extracted. Association of proteoglycans into Sepharose 4B particles gave extraction patterns similar to reassociation into extracted cartilage. These findings are consistent with the hypothesis that proteoglycans are immobilized within cartilage through the formation of aggregates and suggest that retention is dependent upon the integrity of the collagen mesh.

Animals↗
PubMed1981

[Postnatal histogenesis of the cartilage plate of the spinal column -light and electron microscopic observations (author's transl)].

In mice ranging in age from birth to 45 weeks, the cartilage plate in the spinal column was systemically examined by light and electron microscopy. In addition, the proximal end of tibia in 3 week-old mice was studied for comparison. In early life immediately after birth, the nucleus pulposus was separated by cartilage tissue from the ossified vertebral body. The cartilage could be divided into two portions, one portion close to the nucleus pulposus and the other close to the vertebral body. At 1 week, the cartilage toward the nucleus was further divided into two layers, a superficial thin cartilaginous layer close to the nucleus and a deep layer composed of degenerating and degenerated chondrocytes and calcified matrix. After 8 weeks, the deep layer was invaded with numerous irregularly-shaped cavities which contained osteoblasts, osteoclasts and blood vessels. Thus, the deep layer could be considered to be ossified. On the other hand, the cartilage which was near the vertebral body in early life, consisted of chondrocytes which were arranged in column. Thus the cartilage near the vertebral body was thought to be involved in ossification and development of the vertebrated body. From a comparison with the proximal end of tibia, the superficial layer close to the nucleus pulposus, the succeeding deep portion, and the cartilage close to the vertebral body seemed to correspond to the articular cartilage, the secondary ossification center, and the epiphyseal plate of long bones, respectively. Thus, the junction of vertebral bodies was thought to be similar in structure to the joint between long bones. Therefore, the cartilage plate of the spinal column can be regarded to belong to a component of the vertebral body.

Animals↗
PubMedDate not supplied

Histopathological and ultrastructural modifications of the arthrosis articular cartilage.

Thirty samples of articular cartilage taken during the operation from patients with incipient arthrosis, arthrosis with radiological modifications and arthrosis under study for Rheumatoid Arthritis (RA) were investigated using histopathological (HE, VG, PAS-Alcian, Gömöri, Safranine O) and electronmicroscopic techniques. The control material was made of posttraumatic cartilage (Moore prosthesis). Histopathologically, the incipient arthrosis cartilage had superficial exfoliations associated with reduced saframinophilic tinctorial perichondrocytic activity. The arthrosic cartilage with typical radiological modifications was individualized at the synovia-cartilage junction by villous aspects of the synovia associated with perichondrocytic gaps, reduction of safraninophilia and modifications of reticuline-collagenic network. The arthrosic cartilage under study for RA revealed destructive fibrous modifications of the synovia and severe affection of the articular cartilage at synovia-cartilage junction. Electronmicroscopically, the ultrastructural affection was minimum in the incipient arthrosis cartilage developing to chondrocytic degeneration in arthrosis with radiological correspondent. Both histopathological and ultrastructural data emphasize the fact that arthrosis is associated with synovitis following a primitive degenerative process similar to rheumathoid synovitis in arthrosis under study for RA.

Biomarkers↗
PubMed1995

[Morphologic studies of the beginning of vascularization and ossification in human thyroid cartilage].

In contrast to the cartilaginous preformed bones of the skeleton, ossification of human thyroid cartilage begins at the end of the second decade of life. The process continues until an advanced age and shows sex differences. An in-growth of blood vessels by cartilage canals is a prerequisite for ossification. The aim of the study was to investigate the temporal and spatial appearance of cartilage canals in thyroid cartilage. Extracellular matrices of cells in cartilage canals were characterized immunohistochemically. Corrosion casts indicated that the cricothyroid branch of the superior thyroid artery was involved in vascularization of the thyroid cartilage. The first cartilage canals were detectable at the end of puberty, always lying at certain distances to almost ossified areas of the thyroid cartilage. The extracellular matrix localized at the border of the cartilage canals reacted with antibodies against type I collagen and type III procollagen, as well as with antibodies against type II collagen. This finding suggests that these cells are intermediate between fibroblasts and chondrocytes.

Adolescent↗
PubMed1995

Biomechanical properties of hip cartilage in experimental animal models.

The material properties of normal adult articular cartilage were determined in the femoral head and acetabulum of baboons, dogs, and bovines, and were compared with those of normal human hip cartilage. In situ creep and recovery indentation experiments were performed using an automated creep indentation apparatus. To curvefit the entire creep curve, a numerical algorithm based on biphasic finite element methods and nonlinear optimization was developed. This effort represents the first successful use of 100% of the creep indentation curve to obtain the mechanical properties of normal articular cartilage. The results show that material properties of articular cartilage exhibit significant topographical variations in the femoral head and acetabulum, and between these two bone structures. Furthermore, significant differences exist in the mechanical properties of hip cartilage among the 4 species. Specifically, in all species the smallest aggregate modulus is found in the inferior aspect of the femoral head. Among all species, human hip cartilage is the stiffest in all test sites; bovine tissue is the softest. Human tissue has the smallest Poisson's ratio and permeability in all test sites. The aggregate modulus of human hip cartilage is closely resembled by that of baboon hip cartilage. Anatomically, canine and baboon hips exhibit similar characteristics to the human hip joint; the bovine hip joint is distinctly different. Based on this study's data, the baboon represents the most appropriate animal model of normal human hip articular cartilage.

Animals↗
PubMed1994

Factors affecting articular cartilage thickness in osteoarthritis and aging.

OBJECTIVE: To test the hypothesis that both aging and osteoarthritis (OA) contribute to the variance of human articular cartilage thickness of the knee and whether these contributions occur predominantly at weight bearing cartilage sites. METHODS: Thin, sagittal magnetic resonance images (MRI) of both knees were examined in 52 patients with idiopathic OA of the knee of short duration (87%: < or = 4 years) and 40 reference subjects of comparable age and sex distribution. Articular cartilage thickness was measured at the weight bearing and nonweight bearing femoral condylar, tibial plateau, and posterior patellar sites. Multiple regression analyses were performed to examine the influence of OA, age, sex, obesity (body mass index), and bone size on cartilage thickness. RESULTS: Age accounted for a significant linear decrease (p < 0.001) in both lateral and medial weight bearing femoral cartilage thickness of both knees, but failed to account for any significant variance in thickness at other cartilage sites. OA accounted for a significant decrease (p < 0.02) in the thickness of the femoral articular cartilage in the medial and lateral right knee compartments and in the lateral left knee compartment, but not in the medial left knee compartment. Significant cartilage thinning could be detected by MRI in patients with OA, even when the joint space was normal radiographically. CONCLUSION: The asymmetric decrease in the left knee may reflect the effect of mechanical factors. Our data show that articular cartilage thickness decreases at the femoral weight bearing sites both with age and as a consequence of OA and that these contributions can be distinguished from one another.

Adult↗
PubMedDate not supplied

Non-reducible collagen cross-linking in cartilage from broiler chickens with tibial dyschondroplasia.

Recent work has shown that hydroxylysylpyridinoline (HP), a non-reducible cross-link that stabilizes the collagen fibril network, is significantly greater (over 10-fold) in dyschondroplastic cartilage than in normal growth-plate cartilage in the tibiotarsi of chickens with homocysteine-induced tibial dyschondroplasia (TD). In the present study, broiler chicks with a genetic disposition to TD, as well as normal broiler chicks on a copper-deficient diet alone or supplemented with copper and thiram, were raised for 3 to 4 weeks (Expts. 1 and 2). Their dyschondroplastic cartilage from the proximal tibiotarsus was collected and analyzed for HP as well as lysylpyridinoline (LP) cross-links. Normal growth plate cartilage was obtained from chicks on the copper-deficient diet supplemented with copper. In a third experiment, another set of broiler chicks was raised on a corn/soybean meal-based diet with or without homocysteine, and their articular and sternal cartilage were isolated for cross-link analysis. In the first two experiments, dyschondroplastic cartilage from all birds with induced TD had higher HP and LP concentrations than growth-plate cartilage from birds without TD, although the ratios of HP to LP varied. In the third experiment, the sternal and articular cartilage from birds with homocysteine-induced TD appeared normal, having similar HP concentrations in the same types of cartilage in birds without TD.

Amino Acids↗
PubMed1993

Keratan sulfate as a marker of articular cartilage catabolism and joint treatment in ponies.

Keratan sulfate (KS) is a glycosaminoglycan, distribution of which is confined mostly to hyaline cartilage. As such, it is a putative marker of hyaline cartilage catabolism. In experiment 1, a focal osteochondral defect was made arthroscopically in 1 radial carpal bone of 2 ponies, and in 2 other ponies, chymopapain was injected into the radiocarpal joint to induce cartilage catabolism. Sequential and concurrent plasma and synovial fluid concentrations of KS were measured, up to 13 months after induction of cartilage injury, to determine whether changes in KS concentrations reflected cartilage catabolism. In experiment 2, a large, bilateral osteochondral defect was made in the radial carpal bones of 18 ponies, which were subsequently given postoperative exercise and/or injected intra-articularly with 250 mg of polysulfated glycosaminoglycan (PSGAG). Medication was given at surgery, then weekly for 4 weeks. Blood samples were collected and synovial fluid was aspirated before surgery, when medication was given, and at postmortem examination (postoperative week 17). The KS concentration was measured in these fluids to determine whether changes in KS concentration indicated an effect of joint treatment. In experiment 1, the concentration of KS in synovial fluid was highest 1 day after joint injury, and the concentration in plasma peaked 2 days after joint injury. For ponies receiving chymopapain intra-articularly (generalized cartilage catabolism), a fivefold increase over baseline was observed in the concentration of KS in plasma (peak mean, 1.2 micrograms/ml), and a tenfold increase over baseline in synovial fluid (peak mean, 2.0 mg/ml) was observed. On average, these maxima were threefold higher than values in fluids of ponies with osteochondral defects (focal cartilage disease). In experiment 2, nonexercised ponies had lower KS concentration (as a percentage of the preoperative concentration) in synovial fluid than did exercised ponies at all postoperative times, and at postoperative week 17, this effect was significant (P < 0.05). This may be related to decreased turnover of KS in articular cartilage attributable to stall confinement and late increase in turnover related to exercise. Seventeen weeks after surgery, synovial fluid from exercised, medicated ponies had significantly (P < 0.05) higher KS content than did fluid from exercised, nomedicated ponies. This indicated that exercise, when combined with medication, may increase KS release from articular cartilage. Synovial fluid from medicated joints of nonexercised ponies had significantly (P < 0.05) lower KS concentration than did synovial fluid from nonmedicated joints of nonexercised ponies.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1997

Insulin-like growth factor 1 and corticosteroid modulation of chondrocyte metabolic and mitogenic activities in interleukin 1-conditioned equine cartilage.

OBJECTIVE: To evaluate potential stimulatory or matrix-sparing effects of insulin-like growth factor 1 (IGF-1), alone or in combination with a corticosteroid, in an interleukin 1 (IL-1)-induced model of cartilage degradation. SAMPLES: Cartilage from the weightbearing surfaces of trochlea and condyles of clinically normal 2-year-old male horses. PROCEDURE: Triamcinolone acetonide and IGF-1 effects were evaluated by assessing: matrix responses by sulfated glycosaminoglycan (GAG) assay and [35S]sulfated GAG synthesis; collagen content by hydroxyproline assay; and mitogenic response by [3H]thymidine incorporation into DNA and fluorometric assay of total DNA concentration. RESULTS: Conditioning of cartilage explants with 10 ng of human recombinant IL-1 alpha increased degradation and decreased synthesis of matrix proteoglycans (PG), without affecting matrix collagen content. Human recombinant IGF-1 decreased PG loss and reversed the reduction of PG synthesis in cartilage explants conditioned with IL-1. Given alone, steroids decreased PG concentration and synthetic rate in normal cartilage. However, the previously diminished PG content, attributable to IL-1 conditioning, was not further exacerbated by steroid administration in IL-1-conditioned explants. Combined treatment of normal cartilage explants with IGF-1 and steroids resulted in PG preservation and increase in collagen content. Similar PG and collagen effects were not evident when treating IL-1-conditioned cartilage with IGF-1/steroid combinations. Decrease in chondrocyte proliferation was associated with steroid administration. Exposure to IGF and steroids prevented the decrease in mitogenesis that could lead to cellular loss, particularly in IL-1-conditioned explants. CONCLUSION: Combination IGF-1 and steroid treatment of normal cartilage cultures indicated substantial ability to override the anabolic suppression associated with steroids alone. Potentially, administration of corticosteroids, followed by IGF-1, may act to decrease propagation of detrimental mediator release while allowing appreciation of the chondroenhancing effects of IGF-1. These beneficial effects were considerably reduced in IL-1-induced cartilage damage.

Adrenal Cortex Hormones↗
PubMed1997

Evaluation of cartilage lesions on the medial femoral condyle as a cause of lameness in horses: 11 cases (1988-1994).

OBJECTIVE: To evaluate clinical findings and response to treatment in horses in which cartilage lesions on the medial femoral condyle were a cause of lameness. DESIGN: Retrospective case series. SAMPLE POPULATION: Medical records of 11 horses that had cartilage lesions on the medial femoral condyle detected during arthroscopy of the stifle. PROCEDURE: Signalment, history, lameness examination, response to intra-articular anesthesia, radiographs of the stifle, observations during diagnostic arthroscopy, and treatment were extracted from the medical record of each horse. Follow-up examinations and outcome were available for all horses. RESULTS: All horses in the study had lameness, but their gait improved after intra-articular injection of anesthetic. Abnormalities were not observed on radiography of the stifle. Diagnostic arthroscopy was performed on 12 affected joints in 11 horses. Cartilage was dimpled, wrinkled, and infolded, and a blunt arthroscopic probe could be inserted into the subchondral bone. In addition to focal lesions, 4 horses had generalized damage to cartilage on the medial femoral condyle. Focal cartilage lesions on the femoral condyle were debrided. In 2 horses, debridement was not performed because of extensive generalized damage to the cartilage. Six of 7 horses with focal cartilage lesions treated by debridement recovered completely and resumed previous activities. CLINICAL IMPLICATIONS: Cartilage lesions on the medial femoral condyle can cause lameness in performance horses. Diagnostic arthroscopy is necessary to make an accurate diagnosis. Debridement of focal cartilage lesions may allow some horses to successfully resume performance activities.

Animals↗
PubMed1998

Expression of matrix metalloproteinase 7 (matrilysin) in human osteoarthritic cartilage.

Matrix metalloproteinases (MMP) consisting of at least 16 different molecules are thought to be involved in the degradation of extracellular matrix (ECM) macromolecules under various pathologic conditions. Among them, MMP-7 (matrilysin) is unique in that it has high specific activity against various ECM components such as cartilage proteoglycan. In the present study, we examined the expression and tissue localization of MMP-7 in articular cartilages of human osteoarthritis (OA). Immunohistochemistry using a monoclonal antibody specific to MMP-7 demonstrated that the proteinase is localized to the OA chondrocytes mainly in the superficial and transitional zones in 92% of the OA cases examined (36 of 39 cases). On average, approximately 30% of the total chondrocytes (29.1%+/-30.2%) were immunostained in the positive OA cartilage samples. In contrast, MMP-7 staining was found in 8% of the normal cartilage cases (1 of 12 cases), and only a few chondrocytes (0.15%+/-0.67%) in the superficial zone were immunostained. There was a linear correlation between degree (%) of the immunostained chondrocytes and Mankin scores (rho [rho] = 0.84). Immunoblot analysis of the culture media from the cartilage explants demonstrated MMP-7 in 65% of the OA cases (15 of 23 cases) and 8% of the normal specimens (1 of 12 cases). Reverse transcription-PCR demonstrated the specific amplicon in 68% of the OA cartilage cases (17 of 25 cases), whereas only 18% of the control (2 of 11 cases) amplified the product. In situ hybridization revealed that the chondrocytes in OA cartilage express MMP-7 mRNA. MMP-7 gene expression in cultured OA chondrocytes was enhanced by the treatment with interleukin-1alpha and/or tumor necrosis factor-alpha. These data demonstrate for the first time that MMP-7 is overexpressed in human OA cartilage and suggest that cytokine-induced MMP-7 may play an important role in the degradation of ECM macromolecules in the OA cartilage.

Adult↗
PubMed1976

Newer knowledge of the immunology of bone and cartilage.

By the use of modern techniques, the nature of the immunological response to bone and cartilage grafts is becoming clear. Fresh bone, whether cancellous or cortical, will elicit a cell-mediated immunological response; removal of the bone marrow has little effect in reducing immunogenicity. Antibodies against cellular components of the graft are detectable in the recipient only when host and donor have a disparity for the major histocompatibility (H) antigen. Treatment of bone grafts, for the bone bank, by freezing removes their immunogenicity with regard to antibody production but leaves them capable of stimulating the cellmediated immune response. Freeze drying, on the other hand, impairs immunogenicity for both types of responses. Cartilage, grafted alone, is probably non-antigenic as far as both immune responses are concerned and, although there have been a few reports of stimulation of CMI and antibody production by cartilage, these have not been confirmed. Cartilage cells do, however, possess antigens of the major H-antigen system. The cartilage graft is therefore antigenic but only feebly immunogenic, as the matrix proteoglycans protect the cells from the afferent arm of the immune response. Osteoarticular allografts, consisting of both bone and cartilage, sensitize the host due to their bone components. The effect of the immune response upon the bone allograft is to destroy the graft-derived first phase of osteogenesis which, in turn, leads to a poor or non-existent host phase of new bone formation in most allografts. The exact effector mechanism by means of which this destruction is brought about is not known. Bone grafts may be protected from the immune response by use of immunosuppressive measures. Cartilage enjoys a considerable measure of protection from immunological effectors by virtue of its matrix. If this breaks down then the cartilage can become permeable to antibodies. It is suggested that "lymphokines," produced by sensitized lymphocytes, may play some role in destroying the cartilage graft.

Bone Marrow↗
PubMed1976

[Age dependent possibilities for healing in cartilage injuries (experimental investigations with animals) (author's transl)].

Regenerative and degenerative changes of cartilage were studied in animals by micromorphological methods and autoradiography. Cartilage lesions of defined size were set in the femoral condyle of rabbits of variing age by means of an electrical drill developed by us. We used juvenile animals, 3 months old, and senile animals 4 years old. The lesions were studied by lightmicroscopy, electronmicroscopy and scanning electron microscopy. In young animals we were able to demonstrate prevailing reparative changes after injury and the potency for genuine regeneration originating from cartilage. Isolated chondral lesions develop reactive tissue originating mainly from superficial parts of the cartilage. When subchondral bone is exposed we see granulation tissue filling up the defect and change by metaplasia. The replacing tissue originating from superficial cartilage as well as from subchondral bone is able to fill the defect within 3 months. In the replacing tissue originating from cartilage we find fibroblasts and fibrocytes with many mitoses. Consecutively the cells are rounding increasingly. Finally chondrocytes are developing. At the same time as these reparative changes occur we see degenerative changes with decreased mucopolysaccharide synthesis, cell necroses with consecutive decrease in number of cells and singular small cluster. In old animals we could not demonstrate any reparative or regenerative changes after injuries; the artificial defect in cartilage persists. Instead, degenerative changes with signs of arthrosis are developing rapidly: chondroitin sulfate synthesis is decreased, there is ample cluster formation, cell necrosis, decrease in number of cells, and incorporation of paraplasmatic substances in cartilage. We could not demonstrate any mitoses. The causes for the inability of cartilage of aged individuals for reparative changes are discussed.

Age Factors↗
PubMed2003

Characterization of temperature dependent mechanical behavior of cartilage.

BACKGROUND AND OBJECTIVES: Few quantitative studies have investigated the temperature dependent viscoelastic properties of cartilage tissue. Cartilage softens and can be reshaped when heated using laser, RF, or contact heating sources. The objectives of this study were to: (1) measure temperature dependent flexural storage moduli and mechanical relaxation in cartilage, (2) determine the impact of tissue water content and orientation on these mechanical properties, and (3) use these measurements to estimate the activation energy associated with the mechanical relaxation process. STUDY DESIGN/MATERIALS AND METHODS: Porcine nasal septal cartilage specimens (30 x 10 x 2 mm) were deformed using a single cantilever arrangement in a dynamic thermomechanical analyzer. Stress relaxation measurements were made at discrete temperatures ranging from 25 to 70 degrees C in response to cyclic deformation (within the linear viscoelastic region). The time and temperature dependent behavior of cartilage was measured using frequency multiplexing techniques (10-64 Hz), and these results were used to estimate the activation energy for the phase change using the Williams-Landel-Ferry (WLF) equation and the Arrhenius kinetic equation. In addition, the effect of tissue orientation was examined with specimens oriented in both transverse and longitudinal directions at room temperature. RESULTS: The storage moduli of porcine cartilage decreased with increasing temperature, and a critical change in mechanical properties was observed between 58 and 60 degrees C with a reduction in the storage modulus by 85-90%. The shift of the stress relaxation behavior from viscoelastic solid to viscoelastic liquid was observed between 50 and 57 degrees C and likely corresponds to the transition temperature region in which structural changes in the tissue occur. The storage moduli for transverse and longitudinally oriented specimens were 19-22 and 14-16 MPa, respectively at ambient temperature. Reducing the water content (<10% mass loss) by allowing it to dry under ambient conditions resulted in reduction in the storage modulus by 31-36%. The activation energy associated with the mechanical relaxation of cartilage was 147 kJ/mole at 60 degrees C. This value was calculated by measuring stress-strain relationship under conditions where linear viscoelastic behavior was observed (0.09-0.15% of strain) within the transition temperature region (58-60 degrees C). CONCLUSIONS: The anisotropic mechanical behavior of cartilage was quantitatively analyzed in the transversely and longitudinally oriented specimens. Viscoelastic behavior appeared to be strongly dependent on the water content. Using empirically determined estimates of the transition zone temperature range accompanying stress relaxation, the activation energy for stress relaxation was calculated using time and temperature superposition theory and WLF equation. Further investigation of the molecular changes, which occur during laser irradiation, may assist in understanding the thermal and mechanical behavior of cartilage and how the reshaping process might to be optimized.

Animals↗
PubMed1996

An in vitro Model for Studying Mechanisms Underlying Synoviocyte-Mediated Cartilage Invasion in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease of joints involving the pathological development of an invasive and destructive pannus tissue which contributes to the loss of cartilage and bone. To further analyze the process of cartilage degradation and invasion, we have developed an in vitro model composed of cartilage matrix and synoviocytes (isolated from RA pannus tissue, as well as normal synovial membrane). The matrix is derived from pig articular cartilage and contains collagen type II and proteoglycans and is similar in composition to human cartilage. Data generated from this model reveal that synoviocytes isolated from RA pannus tissue invaded cartilage matrix in a manner which directly correlated with the severity of the disease. Analysis of mechanisms associated with the invasive process demonstrate that highly invasive RA synoviocytes maintain a round morphology during attachment and spreading on cartilage matrix, compared with their normal counterparts. Furthermore, the level of secretion of matrix metalloproteinase (MMP) activity was shown to correlate with the RA phenotype, which could be modulated with a novel MMP inhibitor. Normal synoviocytes could be "converted" to an RA phenotype by specific inflammatory cytokines, such that invasion of cartilage matrix was augmented by culturing these cells in the presence of 5 U/ml IL-1b or 18 U/ml TGFb. Invasion was inhibited by 150 U/ml TNFa, and unaffected by 100 ng/ml PDGF. In addition, synovial fluid from RA patients induced invasion of normal synoviocytes, in a concentration dependent manner, from 150% to 460%; however, synovial fluid from another inflammatory arthritidy (Crohn's) did not augment invasion to the same degree. Moreover, this "conversion effect" appears to be specific for synoviocytes, since similar effects could not be achieved with human skin fibroblasts. This in vitro model of synoviocyte-mediated cartilage invasion allows for further molecular characterization of the invasive properties of the synoviocyte which contribute to RA.

Journal Article↗
PubMed2000

Gene expression and immunohistochemical localization of biglycan in association with mineralization in the matrix of epiphyseal cartilage.

This study has used in situ hybridization, Northern blot analysis, and immunohistochemistry at the light and electron microscope levels to localize mRNAs and core proteins of biglycan in developing tibial epiphyseal cartilage of 10-day old Wistar rats. The expression of mRNAs and core proteins of biglycan appeared prominent in hypertrophic and degenerative chondrocytes associated with the epiphyseal ossification centre and the growth plate cartilage, but was not seen in the rest of epiphyseal cartilage. Northern blot analysis confirmed biglycan mRNA expression in the epiphyseal cartilage. Ultrastructural immunogold cytochemistry of the growth plate revealed that prominent immunolabelling was confined to the Golgi apparatus and cisternae of rough-surfaced endoplasmic reticulum of the hypertrophic and the degenerating chondrocytes, the early mineralized cartilage matrices of the longitudinal septum of the lower hypertrophic and the calcifying zones, and fully mineralized cartilage mitrices, which were present in the metaphyseal bone trabeculae. Furthermore, Western blot analysis of biglycan in extracts of fresh epiphyseal cartilage revealed that an EDTA extract, after chondroitinase ABC digestion, contains core proteins of biglycan, indicating the presence of biglycan in mineralized cartilage matrices. These results indicate that the distribution of biglycan is associated with cartilage matrix mineralization.

Animals↗
PubMedDate not supplied

[Gene therapy for cartilage repair].

AIM: Articular cartilage has very limited intrinsic healing capacity. Although numerous attempts to repair full-thickness articular cartilage defects have been conducted, no methods have successfully regenerated long-lasting hyaline cartilage. One of the most promising procedures for cartilage repair is tissue engineering accompanied by gene therapy. METHOD: With gene therapy, genes encoding for therapeutic growth factors can be expressed at a high level in the injured site for an extended period of time. Chondrocytes have been intensively studied for cell transplantation in articular cartilage defects. RESULTS: However, recent studies have shown that chondrocytes are not the only candidate for cartilage repair. Muscle-derived cells have been found capable of delivering genes and represent a good vehicle to deliver therapeutic genes to improve cartilage repair. More importantly, recent studies have suggested the presence of pluripotent stem cells in muscle-derived cells. CONCLUSION: New techniques of cell therapy and molecular medicine for the treatment of cartilage lesions are currently undergoing clinical trials. This paper will summarize the current status of gene therapy for cartilage repair and its future application.

Arthritis, Rheumatoid↗