chondroitin-sulfates and Kashin-Beck-Disease

To evaluate the efficacy and safety of chondroitin sulfate and/or glucosamine hydrochloride in alleviating symptoms and improving the dysfunction of Kashin-Beck disease (KBD) patients.. We undertook a cluster-randomized, placebo-controlled trial in 251 patients with KBD. Participants were randomly allocated to comparing (1) chondroitin sulfate, (2) glucosamine hydrochloride, (3) a combination of chondroitin sulfate and glucosamine hydrochloride, or (4) placebo, for 6 months duration. The primary outcome measures of interest were 20% and 50% reductions in pain from baseline, measured by pain subscale in the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index. Secondary outcome measures included parameters in the WOMAC Index such as pain, stiffness, and physical function, as well as patients' quality of life by the 12-item Short-Form General Health Survey. The trial registration number is ChiCTR-TRC-11001480 (http://www.chictr.org/).. A combination therapy of chondroitin sulfate and glucosamine hydrochloride was effective in reducing WOMAC pain by 20% (differences of 23.4%, P=0.006) and 50% (differences of 15.7%, P=0.016), WOMAC pain (P=0.032), WOMAC stiffness (P=0.043), and WOMAC total score (P=0.035). Chondroitin sulfate used alone was also found to be effective in reducing WOMAC total score and stiffness score (P=0.038 and P=0.023, respectively). No significant positive effects in improving WOMAC Index scores were observed with glucosamine hydrochloride alone.. The findings of this study indicate that a combination of chondroitin sulfate and glucosamine hydrochloride was more effective than placebo in treating KBD.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Chondroitin Sulfates; Drug Therapy, Combination; Female; Glucosamine; Humans; Kashin-Beck Disease; Male; Middle Aged; Pain Measurement; Placebos; Severity of Illness Index; Treatment Outcome; Young Adult

The objective of this study was to investigate the expression of enzymes involved in synthesis and modification of chondroitin sulfate (CS) in knee cartilage tissue of patients with osteoarthritis (OA) and Kashin-Beck disease (KBD).. The knee articular cartilage samples were obtained from 18 age- and gender-matched donors with 6 each in KBD, OA, and control groups. Hematoxylin and eosin (HE) staining, toluidine blue (TB) staining, and immunohistochemical (IHC) staining were performed to estimate the expression level and localization of aggrecan, along with FAM20B, GalT-II, and EXTL2, which are associated with CS synthesis and modification. Rank-based analyses of variance test was used for the multiple comparisons of discrepancy in the positive staining rate among the 3 groups.. In HE and TB staining results, damaged morphology, decreased chondrocyte numbers and proteoglycans were observed in OA and KBD groups compared with the control group. In line with these trends, the positive staining rates of aggrecan were lower in KBD and OA groups than in the control group. Meanwhile, the positive staining rates of CS chain modifying enzymes FAM20B, GalT-II, and EXTL2 decreased in OA and KBD groups.. In conclusion, it was demonstrated that altered expression of CS chain modifying enzymes in OA and KBD groups influenced the synthesis procession of CS and could contribute to the damage of cartilage. Further investigation of these enzymes can provide new theoretical and experimental targets for OA and KBD pathogenesis studies.

Topics: Aggrecans; Cartilage, Articular; Case-Control Studies; Chondrocytes; Chondroitin Sulfates; Galactosyltransferases; Humans; Kashin-Beck Disease; Membrane Proteins; N-Acetylglucosaminyltransferases; Osteoarthritis, Knee; Phosphotransferases (Alcohol Group Acceptor)

To investigate the protective effect of chondroitin sulfate nano-selenium (SeCS) on chondrocyte of Kashin-Beck disease (KBD).. Chondrocyte samples were isolated from the cartilage of three male KBD patients (54-57 years old). The chondrocytes were respectively divided into four groups: (a) control group, (b) SeCS supplement group (100 ng/mL SeCS), (c) T-2 + SeCS supplement group (20 ng/mL T-2 + 100 ng/mL SeCS), and (d) T-2 group (20 ng/mL T-2). Live/dead staining and transmission electron microscopy (TEM) were used to observe cell viability and ultrastructural changes in chondrocytes respectively. Expressions of Caspase-9, cytochrome C (Cyt-C), and chondroitin sulfate (CS) structure-modifying sulfotransferases including carbohydrate sulfotransferase 3, 15 (CHST-3, CHST-15), and uronyl 2-O-sulfotransferase (UST) were examined by quantitative real-time polymerase chain reaction.. After one- or three-days intervention, the number of living chondrocytes in the SeCS supplement group was higher than that in the control group, while it is opposite in the T-2 + SeCS supplement group and T-2 group. The cellular villi number in the surface increased in the SeCS supplement group compared with the control group. Mitochondrial morphology density was improved in the T-2 + SeCS supplement group compared with the T-2 group. Expressions of CHST-3, CHST-15, UST, Caspase-9, and Cyt-C on the mRNA level significantly increased in the T-2 + SeCS supplement group and T-2 group compared with the control group.. SeCS supplement increased the number of living chondrocytes, improved the ultrastructure, and altered the expressions of CS structure-modifying sulfotransferases, Caspase-9, and Cyt-C.

Topics: Biocompatible Materials; Carbohydrate Sulfotransferases; Cartilage, Articular; Caspase 9; Cell Survival; Cells, Cultured; Chondrocytes; Chondroitin Sulfates; Humans; Kashin-Beck Disease; Male; Middle Aged; Mitochondria; Nanostructures; Selenium; Sulfotransferases; Up-Regulation

To investigate selenium (Se) concentrations in serum of patients with rheumatoid arthritis (RA), osteoarthritis (OA), and Kashin-Beck disease (KBD), together with the effect of Se supplement (chondroitin sulfate [CS] nano-Se [SeCS]) on CS structure-modifying sulfotransferases in KBD chondrocyte. Fifty serum samples from each group with aged-matched (40-60 years), normal control (N), RA, OA, and KBD (25 males and females, respectively) were collected to determine Se concentrations. Furthermore, the KBD chondrocytes were divided into two groups following the intervention for 24 h: (a) non-treated KBD group and (b) SeCS-treated KBD group (100 ng/mL SeCS). The ultrastructural changes in chondrocytes were observed by transmission electron microscopy (TEM). Live/dead staining was used to observe cell viability. The expression of CS-modifying sulfotransferases including carbohydrate sulfotransferase 12, 13, and 15 (CHST-12, CHST-13, and CHST-15, respectively), and uronyl 2-O-sulfotransferase (UST) were examined by quantitative real-time polymerase chain reaction and western blotting analysis after SeCS intervention. The Se concentrations in serum of KBD, OA, and RA patients were lower than those in control. In OA, RA, and control, Se concentrations were higher in male than in female, while it is opposite in KBD. In the cell experiment, cell survival rate and mitochondrial density were increased in SeCS-treated KBD groups. Expressions of CHST-15, or CHST-12, and CHST-15 on the mRNA or protein level were significantly increased. Expression of UST slightly increased on the mRNA level, but no change was visible on the protein level. Se deficiency in serum of RA, OA, and KBD was observed. SeCS supplemented in KBD chondrocytes improved their survival rate, ameliorated their ultrastructure, and increased the expression of CS structure-modifying sulfotransferases.

Topics: Adult; Arthritis, Rheumatoid; Chondrocytes; Chondroitin Sulfates; Female; Humans; Kashin-Beck Disease; Male; Middle Aged; Osteoarthritis; Selenium

The objective of this study is to investigate changes in the expression of enzymes involved in chondroitin sulfate (CS) sulfation in distal articular surface of proximal interphalangeal joint isolated from school-age children patients with Kashin-Beck disease (KBD), using normal children as controls. Articular cartilage samples were collected from four normal and four KBD children (7-12 years old), and these children were assigned to control and KBD groups. Hematoxylin and eosin (H&E), toluidine blue (TB), and immunohistochemical (IHC) stainings were utilized to evaluate changes in joint pathology and expression of enzymes involved in CS sulfation, including carbohydrate sulfotransferase 12 (CHST-12), carbohydrate sulfotransferase 13 (CHST-13), and uronyl 2-O-sulfotransferase (UST). The correspondence results were examined by semi-quantitative analysis. Compared with the control group, the KBD group showed the following: a significant decrease of total chondrocytes in superficial, middle, and deep layers and deposition of sulfated glycosaminoglycans in extracellular matrix of KBD cartilage were observed; positive staining chondrocytes of CHST-12, CHST-13, and UST were significantly less in superficial zone of KBD cartilage; and CHST-13 positive staining chondrocytes was reduced in deep zone of KBD cartilage. In contrast, the positive staining rates of CHST-12, CHST-13, and UST in KBD were significantly higher than those in the control group. The decreased expression of these enzymes and the physiologic compensatory reaction may be the signs of early-stage KBD. The alterations of CS structure modifying sulfotransferases in finger articular cartilage might play an important role in the onset and pathogenesis of school-age KBD children.

Topics: Cartilage, Articular; Child; Chondroitin Sulfates; Female; Humans; Kashin-Beck Disease; Male; Osteoarthritis; Selenium; Sulfotransferases

To investigate the expression of enzymes involved in chondroitin sulfate (CS) sulfation in the articular cartilage isolated from adult patients with osteoarthritis (OA) and Kashin-Beck disease (KBD), using normal adults as controls.. Articular cartilage samples were collected from normal, OA and KBD adults aged 38-60 years old, and divided into three groups with six individual subjects in each group. The morphology and pathology grading of knee joint cartilage was examined by Safranin O staining. The localization and expression of enzymes involved in CS sulfation (CHST-3, CHST-11, CHST-12, CHST-13, carbohydrate (N-acetylgalactosamine 4-sulfate 6-O) sulfotransferase 15 - CHST-15, and uronyl 2-O-sulfotransferase - UST) were examined by immunohistochemical (IHC) staining and semi-quantitative analysis.. Positive staining rates for anabolic enzymes CHST-3, CHST-12, CHST-15, and UST were lower in the KBD and OA groups than those in the control group. Meanwhile, reduced levels of CHST-11, and CHST-13 in KBD group were observed, in contrast to those in OA and control groups. The expressions of all six CS sulfation enzymes were less detected in the superficial and deep zones of KBD cartilage compared with control and OA cartilage.. The reduced expression of the CS structure modifying sulfotransferases in the chondrocytes of both KBD and OA adult patients may provide explanations for their cartilage damages, and therapeutic targets for their treatment.

Topics: Adult; Carbohydrate Sulfotransferases; Cartilage, Articular; Case-Control Studies; Chondroitin Sulfates; Female; Humans; Kashin-Beck Disease; Male; Middle Aged; Osteoarthritis; Sulfotransferases

To identify changes in the expression patterns of enzymes involved in chondroitin sulfate (CS) glycosaminoglycan (GAG) metabolism in articular cartilage proteoglycan (PG) isolated from adolescent patients with Kashin-Beck disease (KBD).. Samples of articular cartilage were divided into two groups: Control samples (from five normal children), and KBD samples (from five KBD children) aged 3-12 years old. The morphology and pathology of hand joint cartilage were examined by histochemical staining. The localization and expression patterns of enzymes involved in CS GAG metabolism (i.e., PAPS synthetase 2 (PAPSS2), PAPS transporter 1 (PAPST1), Carbohydrate (N-acetylgalactosamine 4-sulfate 6-O) sulfotransferases 15 (CHST15), Arylsulfatase B (ARSB) and N-acetylgalactosamine-6-sulfate sulfatase (GALNS)) were performed using immuno-histochemical analyses. Positive immunostaining in articular cartilage was semi-quantified.. Reduced aggrecan staining was observed in KBD samples compared with the control samples. The percentages of positive staining for the anabolic enzymes PAPSS2, PAPST1 and CHST15 in the upper and middle zones of KBD samples were significantly lower than that found in the Controls. In contrast, the percentages of positive staining in KBD samples for the catabolic enzymes ARSB and GALNS were significantly higher than the control samples. However, the staining for all of these GAG metabolism enzymes were hardly observed in the deep zones of KBD cartilage, suggesting that significant cell death and necrosis had occurred in this region.. Our results indicate that alterations of enzymes involved in articular cartilage CS GAG metabolism on PGs in the articular cartilage play an important role in the onset and pathogenesis of KBD in adolescent children.

Topics: Aggrecans; Cartilage, Articular; Case-Control Studies; Child; Child, Preschool; Chondroitin Sulfates; Female; Humans; Kashin-Beck Disease; Male; Membrane Glycoproteins; Membrane Transport Proteins; Multienzyme Complexes; Proteoglycans; Sulfate Adenylyltransferase; Sulfate Transporters; Sulfotransferases

To observe the effect of nano-Se-chondroitin sulfate on the growth and apoptosis of chondrocytes from patients with Kashin-Beck disease (KBD) exposed to T-2 toxin in vitro.. Samples of the articular cartilage were obtained from 6 patients with grade II/III KBD diagnosed in line with the National Clinical Diagnostic Criteria of KBD (WS/T 207-2010) for chondrocyte separation and culture in vitro. The separated chondrocytes were treated with synthesized nano-Se-chondroitin sulfate particles and T-2 toxin, alone or in combination, and the cell growth and apoptosis were observed using MTT assay, HE staining and flow cytometry.. The synthesized nano-Se-chondroitin sulfate, with a selenium entrapment ratio of 10.1%, spontaneously formed nanoparticles in distilled water with sizes ranging from 30 to 200 nm. Fourier-transform infrared spectroscopy suggested a possible covalent bond that bound Nano-Se and chondroitin sulfate. Within the concentration range of 50-200 ng/ml, nano-Se-chondroitin sulfate significantly inhibited T-2 toxin-induced apoptosis of the cultured chondrocytes and reduced the early apoptosis rate to (8.64∓1.57)% (P<0.05).. Nano-Se-chondroitin sulfate can inhibit T-2 toxin-induced apoptosis of cultured chondrocytes from KBD patients in vitro, and serves as a promising candidate therapeutic agent for KBD.

Topics: Apoptosis; Cells, Cultured; Chondrocytes; Chondroitin Sulfates; Humans; Kashin-Beck Disease; Middle Aged; Nanostructures; T-2 Toxin

A novel selenium-chondroitin sulfate (SeCS) was synthesized by ultrasonic and dialysis method. With characterization by FTIR, XRD and TEM, the SeCS was found to form nanoparticles in distilled water through a self-aggregation progress. The SeCS nanoparticles had sizes between 30 and 200 nm with selenium entrapment efficiency of about 10.1%. The anti-toxin capacity of SeCS nanoparticles was demonstrated through MTT and apoptosis assays in vitro. Results indicated that the SeCS was less cytotoxic to chondrocytes than sodium selenite. In particular, the SeCS could obviously alleviate chondrocyte apoptosis induced by T-2 toxin compared to chondroitin sulfate. These results thus represent an advanced understanding of the properties of SeCS nanoparticles and demonstrate their exciting potential applications in therapy of Kashin-Beck disease (KBD) and osteoarthritis.

Topics: Apoptosis; Cell Line; Chondrocytes; Chondroitin Sulfates; Humans; Kashin-Beck Disease; Nanoparticles; Osteoarthritis; Selenium