keratan-sulfate and Osteoarthritis--Hip

The aim of this study was to compare the levels of bone and cartilage metabolism markers in the synovial fluid of the hip joint between patients with secondary OA due to osteonecrosis of the femoral head (ONFH), rapidly destructive arthrosis (RDA) and developmental dysplasia of the hip (DDH).. We studied 70 synovial fluid samples obtained from 57 patients with ONFH (mean age 46 years, 34 males, 23 females), 21 samples obtained from 21 patients with RDA (mean age 70 years, 2 males, 19 females) and 20 samples obtained from 20 patients with DDH (mean age 56 years, 2 males, 18 females). The levels of bone alkaline phosphatase (BAP) and tartrate-resistant acid phosphatase 5b (TRACP-5b), as bone metabolism markers, and matrix metalloproteinase 3 (MMP-3) and keratan sulphate (KS), as cartilage metabolism markers, were analysed.. The levels of BAP, MMP-3 and KS were significantly higher in the ONFH group than in the RDA and DDH groups. The levels of TRACP-5b were highest in the RDA group. The levels of BAP in the ONFH group after the development of osteoarthritic changes were significantly lower than those observed in earlier stages. In comparisons between the samples obtained from each group with a terminal condition, the ONFH samples exhibited significantly higher MMP-3 and KS levels, while the TRACP-5 levels were highest in the RDA group.. The ONFH patients showed a relatively bone formative condition before the osteoarthritic stage and maintained a higher rate of cartilage turnover throughout several stages compared with the RDA and DDH patients. RDA patients were characterized by a significantly high osteoclast activity.

Topics: Acid Phosphatase; Adult; Aged; Alkaline Phosphatase; Biomarkers; Cartilage, Articular; Female; Femur Head Necrosis; Hip Dislocation, Congenital; Humans; Isoenzymes; Keratan Sulfate; Male; Matrix Metalloproteinase 3; Middle Aged; Osteoarthritis, Hip; Synovial Fluid; Tartrate-Resistant Acid Phosphatase; Young Adult

The small leucine-rich proteoglycans (SLRPs) modulate tissue organization, cellular proliferation, matrix adhesion, growth factor and cytokine responses, and sterically protect the surface of collagen type I and II fibrils from proteolysis. Catabolism of SLRPs has important consequences for the integrity of articular cartilage and meniscus by interfering with their tissue homeostatic functions.. SLRPs were dissociatively extracted from articular cartilage from total knee and hip replacements, menisci from total knee replacements, macroscopically normal and fibrillated knee articular cartilage from mature age-matched donors, and normal young articular cartilage. The tissue extracts were digested with chondroitinase ABC and keratanase-I before identification of SLRP core protein species by Western blotting using antibodies to the carboxyl-termini of the SLRPs.. Multiple core-protein species were detected for all of the SLRPs (except fibromodulin) in the degenerate osteoarthritic articular cartilage and menisci. Fibromodulin had markedly less fragments detected with the carboxyl-terminal antibody compared with other SLRPs. There were fewer SLRP catabolites in osteoarthritic hip than in knee articular cartilage. Fragmentation of all SLRPs in normal age-matched, nonfibrillated knee articular cartilage was less than in fibrillated articular cartilage from the same knee joint or total knee replacement articular cartilage specimens of similar age. There was little fragmentation of SLRPs in normal control knee articular cartilage. Only decorin exhibited a consistent increase in fragmentation in menisci in association with osteoarthritis. There were no fragments of decorin, biglycan, lumican, or keratocan that were unique to any tissue. A single fibromodulin fragment was detected in osteoarthritic articular cartilage but not meniscus. All SLRPs showed a modest age-related increase in fragmentation in knee articular and meniscal cartilage but not in other tissues.. Enhanced fragmentation of SLRPs is evident in degenerate articular cartilage and meniscus. Specific decorin and fibromodulin core protein fragments in degenerate meniscus and/or human articular cartilage may be of value as biomarkers of disease. Once the enzymes responsible for their generation have been identified, further research may identify them as therapeutic targets.

Topics: Adult; Aged; Aged, 80 and over; Aging; Biglycan; Cartilage, Articular; Case-Control Studies; Chondroitin Sulfate Proteoglycans; Decorin; Extracellular Matrix Proteins; Female; Fibromodulin; Hip Joint; Humans; Keratan Sulfate; Knee Joint; Lumican; Male; Menisci, Tibial; Middle Aged; Osteoarthritis, Hip; Osteoarthritis, Knee; Peptide Fragments; Proteoglycans

To compare concentrations of joint biomarkers in synovial fluid (SF) between idiopathic osteonecrosis of the femoral head (ION) and osteoarthritis (OA) of the hip joint.. Levels of the joint biomarkers cartilage oligomeric matrix protein (COMP), antigenic keratan sulfate (AgKS), and hyaluronan (HA) in SF samples from 21 cases of ION and their relationship to disease stage and history of steroid use were assessed and compared to the result of 29 cases of hip OA.. In both the ION and hip OA groups, levels of COMP and AgKS in SF showed a significant positive correlation. The ION group had significantly higher levels of AgKS in SF than the hip OA group. In the ION group, stage II patients had significantly higher SF levels of both COMP and AgKS than those in stage III patients. No difference in level of HA in hip joint SF was found between steroid and non-steroid treated ION patients or between the stage II and III subgroups.. SF levels of COMP and AgKS may serve as useful joint biomarkers that reflect cartilage metabolism not only in hip OA but also in ION.

Topics: Biomarkers; Cartilage; Cartilage Oligomeric Matrix Protein; Enzyme-Linked Immunosorbent Assay; Extracellular Matrix Proteins; Femur Head Necrosis; Glycoproteins; Humans; Hyaluronic Acid; Joints; Keratan Sulfate; Matrilin Proteins; Osteoarthritis, Hip; Synovial Fluid

To investigate the relationships between serum and urinary molecular markers (MM) used to monitor osteoarthritis.. Forty osteoarthritis patients had blood and urine collected at baseline and 1, 3, 6 and 12 months later. Specimens from 20 controls were obtained twice at a one month interval. The concentration of 14 different markers was determined at each time point and the data were analyzed by statistical methodology.. The markers could be divided by the method of principal components analysis into five clusters of related markers: inflammation markers (C-reactive protein, tumor necrosis receptor type I and tumor necrosis receptor type II, interleukin 6, eosinophilic cationic protein), bone markers (bone sialoprotein, hydroxylysyl pyridinoline, lysyl pyridinoline), putative markers of cartilage anabolism (carboxypropeptide of type II procollagen, hyaluronan, epitope 846) and catabolism (keratan sulfate, cartilage oligomeric matrix protein), and transforming growth factor beta. Three markers (tumor necrosis factor receptor II, cartilage oligomeric matrix protein and epitope 846) from independent clusters discriminated osteoarthritis patients from controls. Inflammation was not a confounding factor in measurement, but a recognizable distinguishing factor in osteoarthritis.. The markers separated into rational groups on the basis of their covariance, a finding with independent biochemical support. The covariance of markers from the same cluster suggests the use of a representative marker from the cluster to reflect changes in osteoarthritis. If multiple markers are being measured within a single cluster, then the use of a weighted cluster 'factor' may be preferable to the separate use of individual markers.

Topics: Amino Acids; Biomarkers; Blood Proteins; C-Reactive Protein; Carboxypeptidases; Case-Control Studies; Epitopes; Extracellular Matrix Proteins; Female; Humans; Hyaluronic Acid; Interleukin-6; Keratan Sulfate; Male; Middle Aged; Osteoarthritis; Osteoarthritis, Hip; Osteoarthritis, Knee; Procollagen; Receptors, Tumor Necrosis Factor; Sialoglycoproteins; Transforming Growth Factor beta

To determine the content and sulfation pattern of keratan sulfate (KS) in synovial fluid (SF) from patients with hip osteoarthritis (OA) and investigate its significance as a marker of cartilage matrix metabolism.. Hip SF samples were aspirated from 50 patients with OA. KS in the samples was digested to 2 disaccharide isomers, beta-galactosyl-(1-4)-6-0-sulfo-N-acetylglucosamine (L2) and beta-6-0-sulfo-galactosyl-(I-4)-6-0-sulfo-N-acetylglucosamine (LA) by keratanase II. Concentrations of these disaccharide isomers were determined by high performance liquid chromatography (HPLC), and their levels were investigated in relation to radiological stage of disease.. Analysis of covariance (age as covariate) showed that the L2 levels in advanced stage OA were significantly lower than in early stage OA (p < 0.0001). L2 levels in terminal stage OA were also significantly lower than in early stage OA (p < 0.0001); however, no significant difference was observed between the L2 levels in advanced and terminal stage OA (p = 0.516). There were no significant differences in the levels of L4, L2 + L4, or the ratio of L4 to L2 at each disease stage.. The levels of KS related disaccharide isomer vary with severity of disease in hip OA. Analysis of these KS related disaccharide isomers by HPLC provides information on both the content and sulfation pattern of KS in SF, reflecting the metabolism of cartilage aggrecan.

Topics: Adult; Aged; Biomarkers; Cartilage; Chromatography, High Pressure Liquid; Disaccharides; Female; Humans; Keratan Sulfate; Male; Middle Aged; Osteoarthritis, Hip; Sulfur; Synovial Fluid

Elevated serum levels of keratan sulfate (KS) and hyaluronate (HA) in patients with osteoarthritis (OA) have been reported. We measured KS and HA in dogs to determine if there was an elevation of these serum glycosaminoglycans in a canine model of OA. A single intraarticular injection of 1 mg of chymopapain into a shoulder joint increased serum KS by tenfold, and HA by less than twofold, in 24 hours. Serum KS and HA levels were 3-5-fold higher in dogs younger than 2 months of age than in older dogs. Serum KS and HA concentrations and synovial fluid KS concentrations were unrelated to spontaneous cartilage degeneration in 1-year-old dogs. Higher KS levels in synovial fluid correlated with higher KS levels in serum (r = 0.54, P less than 0.025). The mean KS concentration in sera of older dogs (greater than 3 years old) with OA was 37% higher than that in disease-free controls, but the difference between the groups was not statistically significant. Thus, elevated levels of serum KS and HA do not appear to have clinical significance in this model of OA.

Topics: Aging; Animals; Chymopapain; Dogs; Female; Glycosaminoglycans; Hyaluronic Acid; Keratan Sulfate; Male; Osteoarthritis, Hip; Predictive Value of Tests; Shoulder Joint; Synovial Fluid