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PubMed2000

Human cartilage glycoprotein 39 (HC gp-39) mRNA expression in adult and fetal chondrocytes, osteoblasts and osteocytes by in-situ hybridization.

OBJECTIVE: To examine the expression pattern of human cartilage glycoprotein 39 (HC gp-39) mRNA in human cartilage and bone. DESIGN: In-situ hybridization analysis was used to examine the expression pattern of human cartilage glycoprotein 39 (HC gp-39) mRNA in adult human osteoarthritic articular cartilage from various stages of disease, as well as in human osteophytic tissue and in human fetal bone. RESULTS: In cartilage from patients with mild osteoarthritic cartilage degeneration, HC gp-39 was expressed at moderate to high levels only in chondrocytes of the superficial zone. In advanced OA cartilage, cloning chondrocytes of the superficial zone expressed high levels of HC gp-39 and chondrocytes of the mid- and deep zones were also positive. HC gp-39 was undetectable in the chondrocytes of normal articular cartilage. In osteophytic tissue, the expression of HC gp-39 mRNA was intense in flattened, end-stage osteoblasts and in primary osteocytes in both endochondral and intramembranous bone formation. Proliferating osteoblasts expressed low to moderate levels. Notably, mature osteocytes were negative for HC gp-39 expression. Chondrocytes in the secondary ossification center of developing fetal cartilage demonstrated high expression while growth plate and mineralized cartilage chondrocytes had lower expression. Osteoblasts at sites of endochondral and intramembranous bone formation were positive for expression of HC gp-39. CONCLUSIONS: The stage-specific expression of HC gp-39 in fetal development and adult remodelling bone and cartilage provides evidence for a specific functional or structural role for HC gp-39 in bone and cartilage tissue. HC gp-39 is expressed in diseased human osteoarthritic cartilage and osteophyte, but not in non-diseased tissue, and its distribution within the tissue changes as disease progresses. OA is characterized not only by cartilage degeneration, but by increased subchondral bone formation and osteophytosis. The results from this study indicate that the increased HC gp-39 expression in OA serum and synovial fluid may reflect not only cartilage degeneration but increased osteogenesis.

Adipokines↗
PubMed2001

Role of cartilage-derived anti-angiogenic factor, chondromodulin-I, during endochondral bone formation.

OBJECTIVE: Cartilage is a typical avasclar tissue that exhibits powerful resistance to angiogenesis or vascular invasion. We previously identified a cartilage-specific 25 kDa glycosylated protein, chondromodulin-I (ChM-I), as anti-angiogenic factor. Taking advantage of ectopic bone formation and xenograft tumour model by human chondrosarcoma cell line OUMS-27, we examined how ChM-I is involved in switching of angiogenesis in cartilage. DESIGN: Gene expression pattern of ChM-I was examined in 4-week-old mice and mouse embryos by northern blot analysis and in situ hybridization. To evaluate the effect of ChM-I on ectopic bone formation, guanidine extracts of demineralized bone matrix were mixed with the ChM-I-bound heparin-Sepharose beads and were implanted onto the fasciae of back muscle of 6-week old nude mice. To analyse the effect of ChM-I on tumour angiogenesis, the level of ChM-I mRNA in cartilaginous tumours was assessed by competitive PCR, and compared with that of articular cartilage. Then, human chondrosarcoma OUMS-27 cells were inoculated into the back of nude mice to form a tumour about 45 mm3 in size. Recombinant ChM-I protein was administrated into OUMS-27 xenograft tumours for the initial 5 days to study its effect against tumour-angiogenesis. RESULTS: ChM-I gene was specifically expressed in cartilage of 4-week-old mice. Eye and thymus were also identified as minor expression sites. However, during endochondral bone development, cartilage changes its character from anti-angiogenic into angiogenic prior to the replacement of calcified cartilage by bone. In embryos, ChM-I mRNA was expressed in proliferative and upper hypertrophic cartilage zones in the developing cartilaginous bone rudiments, but completely abolished in lower hypertrophic and calcified cartilage zones. Purified ChM-I protein apparently inhibited vascular invasion into cartilage induced by the implantation of demineralized bone matrix in nude mice, leading to the inhibition of replacement of cartilage. The level of ChM-I transcripts in the lower-grade chondrosarcomas was substantially reduced to several hundreds or less in the lower-grade chondrosarcomas, compared with that of articular cartilage or other benign cartilage tumours. The local administration of recombinant human ChM-I almost completely blocked tumour angiogenesis and growth in the human chondrosarcoma xenografts in mice. CONCLUSIONS: ChM-I is involved in the anti-angiogenic property of cartilage and its absence creates a permissive microenvironment for vascular invasion into cartilage under physiological and pathological conditions.

Animals↗
PubMed2001

Accumulation of advanced glycation endproducts reduces chondrocyte-mediated extracellular matrix turnover in human articular cartilage.

OBJECTIVE: The prevalence of osteoarthritis (OAs) increases with age and coincides with the accumulation of advanced glycation endproducts (AGEs) in articular cartilage, suggesting that accumulation of glycation products may be involved in the development of OA. This study was designed to examine the effects of accumulation of AGEs on the turnover of the extracellular matrix of human articular cartilage. DESIGN: Chondrocyte mediated cartilage degradation (GAG release, colorimetric) was measured in human articular cartilage of donors aged 19-82 years (N=30, 4-day culture). In addition, to mimic the age-related increase in AGE levels in vitro, cartilage was cultured in the absence or presence of glucose, ribose or threose. Cartilage degradation and proteoglycan synthesis ((35)SO(2)(-4) incorporation) were measured and related to the degree of cartilage AGE levels (fluorescence at 360/460 nm). RESULTS: Chondrocyte-mediated degradation of articular cartilage (i.e. GAG release) decreased with increasing age of the cartilage donor (r=-0.43, P< 0.02). In vitro incubation of cartilage with glucose, ribose or threose resulted in a range of AGE levels that was highly correlated to the chondrocyte-mediated cartilage degradation (r=-0.77, P< 0.001, N=26). In addition, in these in vitro glycated cartilage samples, a decrease in proteoglycan synthesis was observed at increasing AGE levels (r=-0.54, P< 0.005, N=25). CONCLUSIONS: This study shows that an increase in AGE levels negatively affects the proteoglycan synthesis and degradation of articular cartilage. In combination, these two effects reduce the turnover of the cartilage and thereby the maintenance and repair capacity of the tissue. By this mechanism, the age-related increase in cartilage AGE levels may contribute to the development of OA.

Adult↗
PubMed2005

Potential involvement of oxidative stress in cartilage senescence and development of osteoarthritis: oxidative stress induces chondrocyte telomere instability and downregulation of chondrocyte function.

Oxidative stress leads to increased risk for osteoarthritis (OA) but the precise mechanism remains unclear. We undertook this study to clarify the impact of oxidative stress on the progression of OA from the viewpoint of oxygen free radical induced genomic instability, including telomere instability and resulting replicative senescence and dysfunction in human chondrocytes. Human chondrocytes and articular cartilage explants were isolated from knee joints of patients undergoing arthroplastic knee surgery for OA. Oxidative damage and antioxidative capacity in OA cartilage were investigated in donor-matched pairs of intact and degenerated regions of tissue isolated from the same cartilage explants. The results were histologically confirmed by immunohistochemistry for nitrotyrosine, which is considered to be a maker of oxidative damage. Under treatment with reactive oxygen species (ROS; 0.1 micromol/l H2O2) or an antioxidative agent (ascorbic acid: 100.0 micromol/l), cellular replicative potential, telomere instability and production of glycosaminoglycan (GAG) were assessed in cultured chondrocytes. In tissue cultures of articular cartilage explants, the presence of oxidative damage, chondrocyte telomere length and loss of GAG to the medium were analyzed in the presence or absence of ROS or ascorbic acid. Lower antioxidative capacity and stronger staining of nitrotyrosine were observed in the degenerating regions of OA cartilages as compared with the intact regions from same explants. Immunostaining for nitrotyrosine correlated with the severity of histological changes to OA cartilage, suggesting a correlation between oxidative damage and articular cartilage degeneration. During continuous culture of chondrocytes, telomere length, replicative capacity and GAG production were decreased by treatment with ROS. In contrast, treatment with an antioxidative agent resulted in a tendency to elongate telomere length and replicative lifespan in cultured chondrocytes. In tissue cultures of cartilage explants, nitrotyrosine staining, chondrocyte telomere length and GAG remaining in the cartilage tissue were lower in ROS-treated cartilages than in control groups, whereas the antioxidative agent treated group exhibited a tendency to maintain the chondrocyte telomere length and proteoglycan remaining in the cartilage explants, suggesting that oxidative stress induces chondrocyte telomere instability and catabolic changes in cartilage matrix structure and composition. Our findings clearly show that the presence of oxidative stress induces telomere genomic instability, replicative senescence and dysfunction of chondrocytes in OA cartilage, suggesting that oxidative stress, leading to chondrocyte senescence and cartilage ageing, might be responsible for the development of OA. New efforts to prevent the development and progression of OA may include strategies and interventions aimed at reducing oxidative damage in articular cartilage.

Aged↗
PubMed2001

MR imaging and T2 mapping of femoral cartilage: in vivo determination of the magic angle effect.

OBJECTIVE: The purpose of this study was to perform a quantitative evaluation of the effect of static magnetic field orientation on cartilage transverse (T2) relaxation time in the intact living joint and to determine the magnitude of the magic angle effect on in vivo femoral cartilage. MATERIALS AND METHODS: Quantitative T2 maps of the femoral-tibial joint were obtained in eight asymptomatic male volunteers using a 3-T magnet. Cartilage T2 profiles (T2 vs normalized distance from subchondral bone) were evaluated as a function of orientation of the radial zone of cartilage with the applied static magnetic field (B(0)). RESULTS: At a normalized distance of 0.3 from bone, cartilage T2 is 8.6% longer in cartilage oriented 55 degrees to B(0) compared with cartilage oriented parallel with B(0). Greater orientation variation is observed in more superficial cartilage. At a normalized distance of 0.6, cartilage T2 is 18.3% longer. The greatest orientation effect is observed near the articular surface where T2 is 29.1% longer at 55 degrees. CONCLUSION: The effect of orientation on cartilage T2 is substantially less than that predicted from prior ex vivo studies. The greatest variation in cartilage T2 is observed in the superficial 20% of cartilage. Given the small orientation effect, it is unlikely that the "magic angle effect" accounts for regional differences in cartilage signal intensity observed in clinical imaging. We hypothesize that regional differences in the degree of cartilage compression are primarily responsible for the observed regional differences in cartilage T2.

Adult↗
PubMed1975

Ultrastructure of canine articular cartilage: comparison of normal and degenerative (osteoarthritic) hip joints.

Normal canine hip cartilage was compared with cartilage from the degenerative lesions found in young dogs with canine hip dysplasia. The upper 0.5 mm of normal cartilage was characterized. Four distinct layers or zones were found: a layer of fine fibrous material covering the surface, a layer (surface layer) of small (32 nm diameter or less) collagen fibrils tightly packed in bundles and oriented parallel to the surface, a layer (upper layer) or less tightly packed collagen fibrils oriented mostly parallel to the surface with about 33% of the fibrils 64 nm or more, and a layer (intermediate layer) of randomly oriented fibrils with more than 50% of the fibrils 64 nm or larger. Fibril density was high in the surface layer and decreased with depth into the cartilage. In a moderately advanced lesion of degenerative cartilage, there was a layer of amorphous material over the surface. The tightly packed surface layer of small fibrils was absent. The surface itself was uneven and fissued. At depths from the surface comparable to the upper and the intermediate layers in normal cartilage, the proportion of large fibrils was less than in normal cartilage. The overall density of fibrils in degenerative cartilage increased with depth into the tissue. Cells flattened parallel to the surface, with relatively large nuclei, were found in the upper layer of normal cartilage. Cells in the intermediate layers were larger and round. The oblong cells of the upper layer of normal cartilage were not found in any layer of degenerative cartilage. Differences between cells in other layers of normal and degenerative cartilages were minimal. A model for the arrangement of chondrocytes and collagen fibrils for normal and degenerative cartilage was proposed. Ultrastructural changes in degenerative cartilage were prominent in the upper 0.5 mm of cartilage. These changes were changes in the number of collagen fibrils/mum-2 and a change from a characteristic pattern of collagen fibril diameters and orientation found in normal tissue.

Animals↗
PubMed2006

[Treatment of deep cartilage defects of the knee with autologous chondrocyte transplantation on a hyaluronic Acid ester scaffolds (Hyalograft C)].

PURPOSE OF THE STUDY: The treatment of chondral defects by transplantation of autologous chondrocytes has recently shown further development. Various biomaterials are used as carriers facilitating attachment and even distribution of chondrocytes in the defect. Since 2003 Hyalograft C, hyaluronan-based scaffolds, has been used, in a clinical study, for implantation of autologous chondrocytes in the treatment of deep chondral lesions of the knee at our department. MATERIAL: Eight patients (7 men and 1 woman; average age, 31 years) followed up for at least 9 months were evaluated. The lesions with an average size of 3.9 cm2 were localized on femoral condyles. METHODS: The outcome of surgery was evaluated on the basis of the IKDC Subjective Knee Evaluation Form, Knee Injury and Osteoarthritis Outcome Score (KOOS) and Lysholm knee score. The patients underwent MR examination preoperatively and at 3, 6 and 12 months after surgery. The newly-formed cartilage was assessed by International Cartilage Repair Society (ICRS) visual scores at second-look arthroscopy carried out at 9 to 12 months following transplantation. Consistency of the new cartilage developing in the defect and that of healthy cartilage around the defect was compared by means of a special indentation probe in three patients. A biopsy sample was collected from the grafted site for histological, histochemical and immunohistochemical examination. RESULTS: All patients reported improvement in knee function on average at 10 months after surgery. The average IKDC subjective score increased from 46 points preoperatively to 74 points postoperatively. The KOOS evaluation showed pain relief and improved function. In quality of life evaluation the average score of 35 points before surgery increased to 70 points after it. The average Lysholm knee score was 61 points before and 83 points after surgery. MR findings correlated well with arthroscopic findings. Second-look arthroscopy showed a normal appearance of the newly-formed cartilage in six, and an abnormal appearance in two patients. The average ICRS visual score was 9.4 points. No graft failure was recorded. The newly-produced tissue had the histological characteristics of a mixed hyaline and fibrous cartilage in seven patients, and of hyaline-like cartilage in one patient. DISCUSSION: The ICRS visual repair assessment of the newly-formed tissue showed that our results were better than the one-year outcomes reported by Bartlett et al. (11 patients after transplantation of a collagen bilayer seeded with chondrocytes), but worse than the results of an Italian multi-center study (55 patients with Hyalograft C-based grafts followed up on average for 14 months). At almost one year, implantation of on a Hyalograft C resulted in the production of mixed cartilage incorporated well in the subchondral bone. Only one patient had mature hyaline cartilage. One year is too short to allow for complete remodeling of the newly formed cartilage into a mature hyaline cartilage. This is in agreement with other studies suggesting that the new cartilage continues to mature and remodel for a time longer than one year. CONCLUSIONS: Based on our results we suggest that the use of Hyalograft C is a safe and effective option for treatment of deep chondral defects of the knee; it is particularly useful in patients in whom the primary defect treatment has failed. The application of Haylograft C is relatively quick and easy; this is convenient when surgery involves more than one procedure (ligament reconstruction, osteotomy). However, a definite evaluation of this method will be possible only after long-term results are available. Key words: deep cartilage defects, chondral defects, cartilage repair, autologous chondrocyte transplantation, hyaluronan- based scaffold, Hyalograft C, cartilage repair assessment, ICRS.

Adult↗
PubMed1997

Expression of membrane-type 1 matrix metalloproteinase and activation of progelatinase A in human osteoarthritic cartilage.

Matrix metalloproteinases (MMPs) are expressed in osteoarthritic (OA) cartilage and are thought to be involved in the degradation of cartilage extracellular matrix (ECM). Among these proteinases, MMP-2 (gelatinase A) demonstrates a wide range of substrate specificity against the ECM present in cartilage. Although MMP-2 expression increases in OA cartilage, the activation mechanism of the corresponding zymogen (pro-MMP-2) in cartilage is unknown. In this study, we examined the expression pattern of membrane-type 1 MMP (MT1-MMP) in human OA articular cartilage and its correlation with the activation of pro-MMP-2. Immunohistochemical studies demonstrate that MT1-MMP localizes to the chondrocytes in the superficial and transitional zones in all of the samples examined directly correlating with cartilage degradation. Reverse transcription polymerase chain reaction confirmed the predominant expression of MT1-MMP mRNA in the OA cartilage. In situ hybridization revealed the site of expression of MT1-MMP in OA cartilage to be the chondrocytes. Through gelatin zymography and a sandwich enzyme immunoassay it was demonstrated that OA cartilage explants secrete significantly higher levels of pro-MMP-2 than normal samples. Pro-MMP-2 activation was enhanced in the OA cartilage samples and correlated with MT1-MMP expression in the cartilage. Plasma membranes prepared from cultured chondrocytes with MT1-MMP expression and those directly isolated from OA cartilage could activate pro-MMP-2. MT1-MMP gene expression in cultured chondrocytes was induced by treatment with interleukin-1 alpha and/or tumor necrosis factor-alpha. These data suggest that cytokine-induced MT1-MMP in the chondrocytes may play a key role in the activation of pro-MMP-2 in the OA articular cartilage, leading to cartilage destruction through ECM degradation.

Aged↗
PubMed1998

Age-related changes in the articular cartilage of human sacroiliac joint.

Iliac and sacral articular cartilage of 25 human sacroiliac joints (1-93 years) are examined by light microscopy and immunohistochemistry in order to gain further insight into the nature and progress of degenerative changes appearing during aging. These changes can already be seen in younger adults as compared to cartilage degeneration known in other diarthrodial joints. Structural differences between sacral and iliac cartilage can already be observed in the infant: the sacral auricular facet is covered with a hyaline articular cartilage, reaching 4 mm in thickness in the adult and staining intensely blue with alcian blue at pH1. Iliac cartilage of the newborn is composed of a dense fibrillar network of thick collagen bundles, crossing each other at approximately right angles. A faint staining with alcian blue suggests a low content of acidic glycosaminoglycans. In the adult, iliac cartilage becomes hyaline and its maximal thickness reaches 1-2 mm. Both articular facets exhibit morphological changes during aging that are more pronounced in the iliac cartilage and resemble osteoarthritic degeneration; the staining pattern of the extracellular matrix becomes inhomogenous, chondrocytes are arranged in clusters and the articular surface develops superficial irregularities and fissures. Sometimes fibrous tissue fills up these defects. Nevertheless, large areas of iliac cartilage remain hyaline in nature. Sacral articular cartilage often remains largely unaltered until old age. The sacral subchondral bone plate is usually thin and shows spongiosa trabeculae inserted at right angles, suggesting a perpendicular load on the articular facet. Iliac subchondral spongiosa shows no definite alignment and joins the thickened subchondral bone plate in an oblique direction. The iliac cartilage therefore seems to be stressed predominantly by shearing forces, arising from the changing monopodal support of the pelvis during locomotion. The subchondral bone plate on both the iliac and sacral auricular facet is penetrated by blood vessels that come into close contact with the overlying articular cartilage. These vessels may contribute to the high incidence of rheumatoid and inflammatory diseases in the human sacroiliac joint. Immunolabelling with an antibody against type II collagen reveals a diminished immunoreactivity in the upper half of adult sacral cartilage and only a faint and irregular labelling in the iliac cartilage. Type I collagen can be detected in a superficial layer on the sacral articular surface and around chondrocyte clusters in iliac cartilage, as in dedifferentiating chondrocytes during the development of osteoarthritis.

Adolescent↗
PubMed1975

Influence of the pericellular environment on the cells. The role of mucopolysaccharides in the protection of cartilage cells against immune reactions.

Problems related to rheumatoid arthritis have been investigated by a group at Cambridge using the organ culture technique. Since auto-allergic reactions may be concerned in the chronicity of the disease, the effects of reactive complement-sufficient antisera (AS+C') on embryonic and post-foetal cartilage were examined. The cartilaginous limb bone rudiments enlarged to several times their original volume in control medium, but in the presence of AS+C' they gradually disintegrated, owing to the breakdown of the cartilage matrix; only the superficial cells of the enveloping soft connective tissue were killed, however. Provided breakdown had not advanced too far, the effects of AS+C' were reversible. It was not clear how AS+C' produced these changes, since cartilage matrix is impermeable to molecules as large as the immunoglobulins. To find whether there was a difference in permeability between embryonic and post-foetal cartilage, similar experiments were made on the articular cartilage of young pigs. AS+C' had no effect on pure articular cartilage, and it was shown immunohistochemically that IgG did not penetrate beyond the most superficial layer of cartilage. When, however, the explant was associated with soft connective tissue either as invading marrow or as an adjacent explant of synovium, the cartilage matrix was depleted of proteoglycan; IgG antibodies then entered the cartilage and reacted with the chondrocytes. After a lapse of 8-10 days, collagen also began to break down. If the degradation of collagen was not too extensive, the changes were reversible. Pure cartilage was depleted of proteoglycan by trypsinization and then cultivated in AS+C'. All the chondrocytes reacted with the IgG antibodies. The peripheral cells were killed, but those in the interior survived and rapidly secreted pericellular capsules rich in proteoglycan, which shielded them from further contact with antibodies. In other experiments, pure cartilage was associated with a synovial explant and cultivated in AS+C' for 10 days; this caused severe depletion of the matrix. The synovial tissue was then removed and the isolated cartilage cultured for a further 10 days in either AS+C' or control medium. If mainly proteoglycan had been lost during the primary culture period, breakdown did not continue in AS+C', and sometimes a little new matrix was regenerated, though less than in control medium; if, however, the collagen had been extensively degraded, breakdown continued even in control medium. It is suggested that in both the embryonic and post-foetal cartilage, degradation of the cartilage matrix was due to the enzymatic activity of the associated soft connective tissue which caused a loss first of proteoglycan, which enabled antibodies to reach the chondrocytes, and then of collagen. The possible relevance of these results to the pathogenesis of rheumatoid arthritis is discussed.

Animals↗
PubMed1998

[Tissue engineering of hyaline cartilage].

OBJECTIVE: To study the new way to repair the defect of the articular cartilage. METHOD: The articular-epiphyseal cartilage complexes from 8 newborn rabbits were enzymatically dissolved, and the chondrocytes were seeded onto the fibrous chitin mesh in a 96-well plate in DMEM medium. RESULT: Cultured for 21 days, the "membrane-like cartilage" was strong enough to be transferred. At the 110th day, the semitransparent cartilage discs were 4.4 mm in diameter and 14.8 mg in weightness. Staining of SatranO showed that engineered "cartilage" was bound of GAGs and the chondrocytes expressed the mRNA of type II collagen by in situ hybridization, which is resemble to that of the normal hyaline cartilage beside the biodegraded fibrous chitin embedded in. The "membrane-like cartilage" cultured for 21 days was grafted into the articular cartilage defects of knee of adult rabbits. Seven of 9 defects healed with new cartilage and the structure was well organized in 16 weeks. CONCLUSION: The biodegradable fibrous chitin is a good "matrix" for cartilage tissue engineering. The engineered "cartilage" is true hyaline cartilage, which is a new "alive cartilage tissue" for the repairment of the defect of articular cartilage.

Animals↗
PubMedDate not supplied

Autologous cartilage grafts enhanced by a novel transplant medium using fibrin sealant and fibroblast growth factor.

OBJECTIVE: To introduce and assess a system for the delivery of fibroblast growth factor to autologous cartilage grafts using fibrin sealant and analyze whether this "enhancement" results in reduced rates of cartilage resorption and greater preservation of normal architectural features compared with "unenhanced" cartilage grafts. METHODS: Auricular cartilage segments measuring 1 cm(2) were harvested from 12 New Zealand white rabbits, morselized, and implanted into the subcutaneous dorsum of the upper back for 3 months. The conditions included (1) cartilage alone; (2) cartilage + fibrin sealant; (3/4) cartilage + acidic or basic fibroblast growth factor (aFGF or bFGF); and (5/6) cartilage + fibrin sealant + aFGF or bFGF. Subsequent to graft harvest, gross and microscopic assessments were performed to assess size, structural integrity, and architectural features, with comparisons performed between each of the conditions. RESULTS: The mean areas of the harvested cartilage grafts treated with fibrin sealant + aFGF or bFGF were 1.23 cm(2) and 1.19 cm(2), respectively, while the corresponding value for the untreated (ie, cartilage alone) specimens was 1.03 cm(2). The percentage of decrease in size was 45% for the untreated specimens and 0% for the specimens treated with fibrin sealant + aFGF or fibrin sealant + bFGF. Cartilage treated with fibrin sealant + bFGF had the greatest quantity of elastin fibers of the 6 conditions. Cartilage grafts treated with fibrin sealant alone demonstrated the most intense ground substance staining on a computerized measure of pixel intensity. CONCLUSIONS: Our findings demonstrated significant improvements in graft quality using fibroblast growth factor and fibrin sealant or even fibrin sealant alone. These findings may justify changes in how cartilage grafts are prepared and delivered for facial augmentation procedures to reduce graft resorption and maintain the structural integrity of the cartilage. Further trials will be performed to elucidate the optimal growth factor concentrations for maximum structural and architectural benefits.

Animals↗
PubMed2001

Age-related decrease in susceptibility of human articular cartilage to matrix metalloproteinase-mediated degradation: the role of advanced glycation end products.

OBJECTIVE: Progressive destruction of articular cartilage is a hallmark of osteoarthritis (OA) and rheumatoid arthritis (RA). Age-related changes in cartilage may influence tissue destruction and thus progression of the disease. Therefore, the effect of age-related accumulation of advanced glycation end products (AGEs) on cartilage susceptibility to proteolytic degradation by matrix metalloproteinases (MMPs) present in synovial fluid (SF) of OA and RA patients was studied. METHODS: Cartilage was incubated with APMA-activated SF obtained from OA or RA patients, and tissue degradation was assessed by colorimetric measurement of glycosaminoglycan (GAG) release. Cartilage degradation was related to the level of AGEs in cartilage from donors of different ages (33-83 years) and in cartilage with in vitro-enhanced AGE levels (by incubation with ribose). MMP activity in SF was measured using a fluorogenic substrate. AGE levels were assessed by high-performance liquid chromatography measurement of the glycation product pentosidine. RESULTS: In cartilage from donors ages 33-83 years, a strong correlation was found between the age-related increase in pentosidine and the decrease in MMP-mediated tissue degradation (r = -0.74, P < 0.0005). Multiple regression analysis showed pentosidine to be the strongest predictor of the decreased GAG release (P < 0.0005); age did not contribute (P > 0.8). In addition, decreased MMP-mediated GAG release was proportional to increased pentosidine levels after in vitro enhancement of glycation (r = -0.27, P < 0.01). This was demonstrated for both OA and RA SF (for control versus glycated, P < 0.002 for all SF samples tested). CONCLUSION: Increased cartilage AGEs resulted in decreased cartilage degradation by MMPs from SF, indicating that aged cartilage is less sensitive than young cartilage to MMP-mediated cartilage degradation, such as occurs in OA and RA. Therefore, the level of cartilage glycation may influence the progression of these diseases.

Adult↗
PubMed2003

Synthesis of insulin-like growth factor binding protein 3 in vitro in human articular cartilage cultures.

OBJECTIVE: To quantify the rate of synthesis of insulin-like growth factor binding protein 3 (IGFBP-3) and insulin-like growth factor 1 (IGF-1) by in vitro cultures of normal and osteoarthritic (OA) human articular cartilage. METHODS: Levels of IGF-1 and IGFBP-3 in media from in vitro cultures of human cartilage were determined by radioimmunoassay (RIA). IGFBPs were characterized by immunoblots and ligand blots. Ultrafiltration and RIA analysis of synovial fluid (SF) samples and washings of cartilage samples ex vivo were used to calculate partition coefficients and to estimate the amount of IGF-1 and IGFBP-3 in cartilage in vivo. RESULTS: OA cartilage synthesized 150 ng of IGFBP-3 per gm of cartilage per day, compared with 50 ng synthesized by normal cartilage. The surface zone of normal cartilage produced more IGFBP-3 than did the deep zone. Immunoblots and ligand blots confirmed the presence of IGFBP-3. IGFBP-3 synthesis was stimulated by exogenous IGF-1. No freshly synthesized IGF-1 was detected. The quantities of IGF-1 and IGFBP-3 present ex vivo were 11.3 and 78.7 ng/gm of cartilage in normal cartilage and 21.6 and 225.4 ng/gm in OA cartilage. CONCLUSION: The results show that while IGFBP-3 is synthesized in explant cultures, IGF-1 is not. The rate of IGFBP-3 synthesis is 3 times higher in OA than in normal cartilage. Both IGFBP-3 and IGF-1 penetrate into cartilage from SF in vivo. We estimate that the quantities of IGFBP-3 produced in culture by human cartilage are small compared with the amount supplied in the form of "small complexes" from the circulation. The high value of the partition coefficient of IGFBP-3 implies binding to the matrix.

Adult↗
PubMed2005

The relationship between cartilage loss on magnetic resonance imaging and radiographic progression in men and women with knee osteoarthritis.

OBJECTIVE: To determine the relationship between radiographic progression of joint space narrowing and cartilage loss on magnetic resonance imaging (MRI) in patients with symptomatic knee osteoarthritis (OA), and to investigate the location of MRI-based cartilage loss in the knee and its relation to radiographic progression. METHODS: Two hundred twenty-four men and women (mean age 66 years) were studied. Radiographs and MRI of the more symptomatic knee were obtained at baseline and at 15- and 30-month followup. Radiographs of the knee (with weight-bearing) were read for joint space narrowing (scale 0-3), with progression defined as any worsening in score. We used a semiquantitative method to score cartilage morphology in all 5 regions of the tibiofemoral joint, and defined cartilage loss as an increase in score (scale 0-4) at any region. We examined the relationship between progression of joint space narrowing on radiographic images and cartilage loss on MRI, using a generalized estimating equation proportional odds logistic regression, adjusted for baseline cartilage score, age, body mass index, and sex. The medial and lateral compartments were analyzed separately. RESULTS: In the medial compartment, 104 knees (46%) had cartilage loss detected by MRI. The adjusted odds ratio was 3.7 (95% confidence interval 2.2-6.3) for radiographic progression being predictive of cartilage loss on MRI. However, there was still a substantial proportion of knees (80 of 189 [42%]) with cartilage loss visible on MRI when no radiographic progression was apparent. Cartilage loss occurred frequently in the central regions of the femur and tibia as well as the posterior femur region, but radiographic progression was less likely to be observed when posterior femur regions showed cartilage loss. Radiographic progression appeared specific (91%) but not sensitive (23%) for cartilage loss. Overall findings were similar for the lateral compartment. CONCLUSION: While our results provide longitudinal evidence that radiographic progression of joint space narrowing is predictive of cartilage loss assessed on MRI, radiography is not a sensitive measure, and if used alone, will miss a substantial proportion of knees with cartilage loss.

Aged↗
PubMed1991

Ischemic necrosis of cartilage in spontaneous and experimental lesions of osteochondrosis.

This study was designed to examine the association of spontaneous lesions of osteochondrosis with vascular supply to epiphyseal cartilage, and to determine whether similar lesions could be experimentally reproduced by selective interruption of cartilage canal blood supply. The vascular supply to the articular-epiphyseal cartilage complex of the distal end of the femur was studied in 27 microfil- or barium-injected and cleared specimens and 24 serially sectioned microangiographic specimens from 27 clinically normal female swine (3.6 to 71.0 kg). Blood vessels supplying the articular-epiphyseal cartilage complex were consistently restricted to the epiphyseal region and the number of vessels decreased as the pigs increased in weight (p less than 0.001). Spontaneous lesions of osteochondrosis (i.e., cartilage necrosis) were initially seen in the first areas of epiphyseal cartilage to become avascular and were associated with necrotic blood vessels. The number and size of foci of necrotic cartilage increased as the pigs increased in weight (p less than 0.001). Blood supply to epiphyseal cartilage from cartilage canal vessels was surgically interrupted in a highly vascular area of the medial femoral condyle in eight additional 23-kg female swine. This procedure resulted in necrosis of blood vessels within cartilage canals followed by necrosis of surrounding cartilage, lesions that appeared to be identical to early spontaneous lesions of osteochondrosis. These results suggest that the viability of epiphyseal cartilage in the articular-epiphyseal cartilage complex is highly dependent on an adequate blood supply from cartilage canal vessels, and strongly implicates a defect in blood supply in the pathogenesis of osteochondrosis.

Animals↗
PubMed1995

Modulated expression of type X collagen in Meckel's cartilage with different developmental fates.

Mammalian Meckel's cartilage undergoes regionally diverse histodifferentiation: the caudal end of Meckel's cartilage extends to the developing ear and gives rise to malleus and incus through endochondral ossification while its major distal region differentiates into sphenomandibular ligament and the anterior ligament of the malleus tympanic plate through fibrous transformation. Since the entire Meckel's cartilage develops up to chondrocyte hypertrophy, the regional extracellular matrix components in the hypertrophic Meckel's cartilage may differ in association with the diverse developmental fates. In this project, the expressions of cartilage collagens were investigated in developing rat Meckel's cartilage and particular interest was given to type X collagen. A cDNA, HP114, encoding the NC1 domain of rat alpha 1(X) collagen was cloned, and a synthetic peptide based on the sequence deduced from HP114 was used to generate a monospecific antibody. In situ hybridization of newborn rat condylar and angular cartilages undergoing endochondral ossification showed restricted labeling with the alpha 1(X) collagen probe in the hypertrophic chondrocyte layer. In contrast, the alpha 1(X) collagen probe totally failed to label the major distal portion of Meckel's cartilage even in the hypertrophic cartilage zone. Immunohistochemistry using the anti-type X collagen monospecific antibody consistently failed to recognize the epitope in the corresponding portion of Meckel's cartilage throughout the experimental periods of gestational Day 17, newborn, and Postnatal Day 7, while the strictly localized positive staining was found in the posterior part of Meckel's cartilage which gave rise to malleus and incus. Since major cartilage collagens type II and type IX were found to be present throughout Meckel's cartilage, we postulate that the regulatory molecular mechanism of type X collagen expression may be closely associated with the developmental fates of fibrous transformation and endochondral ossification in mammalian Meckel's cartilage.

Amino Acid Sequence↗
PubMed1977

Phosphomonoesterases in growth cartilages of the rat.

Epiphyseal plate cartilage, epiphyseal cartilage, synchondroseal cartilage and mandibular condylar cartilage were studied morphologically and histochemically in 14 days old rats. Ordinary decalcified paraffin sections were stained with hematoxylin & eosin, van Giesons connective tissue stain, or toluidine blue, and used for morphological studies of the different cartilaginous structures. Undecalcified cryostat sections were used for demonstration of acid and alkaline phosphatase. The enzyme activity was tested for at regular intervals during incubation from 15 sec to 120 min. The morphologic study revealed that a marked similarity of construction exists between epiphyseal plate cartilage and synchrondroseal cartilage. The construction of epiphyseal and condylar cartilage differ from that of the other two structures and also differ mutually. With small variations the reaction for both alkaline and acid phosphatase was found to be identical in the zones of erosion, hypertrophy and maturation of the four structures. Intercellularly, acid phosphatase is present in all zones in the synchondroseal and the epiphyseal plate cartilage, while in the epiphyseal and condylar cartilages it is only present in the zones of erosion, hypertrophy and maturation. The identical reaction for acid phosphatase in the epiphyseal and the condylar cartilage is thought, in all likelihood, to be accidental. When kinetic conditions are taken into account, epiphyseal cartilage seems to react like epiphyseal plate and synchondroseal cartilage, while the condylar cartilage takes up an exceptional position among growth cartilages.

Acid Phosphatase↗