chondroitin-sulfates and Bone-Diseases

Topics: Animals; Bone Diseases; Cell Division; Chondroitin Sulfates; Cloning, Molecular; Crystallography, X-Ray; Gene Expression Regulation, Enzymologic; Glucuronosyltransferase; Glycosaminoglycans; Heparan Sulfate Proteoglycans; Humans; Membrane Proteins; Multifunctional Enzymes; Mutation; N-Acetylgalactosaminyltransferases; N-Acetylglucosaminyltransferases; Recombinant Proteins; Substrate Specificity

Topics: Animals; Bone Diseases; Cartilage; Centrifugation, Density Gradient; Chemical Phenomena; Chemistry; Chondroitin Sulfates; Humans; Hyaluronic Acid; Joint Diseases; Keratan Sulfate; Proteoglycans

Knee bone curvature assessed by MRI was associated with OA cartilage loss. A recent knee OA trial demonstrated the superiority of chondroitin sulfate over celecoxib (comparator) at reducing cartilage volume loss (CVL) in the medial compartment (condyle). The main objectives were to identify which baseline bone curvature regions of interest (BCROI) best associated with CVL and investigate whether baseline BCROI and 2-year change are correlated with the protective effect of chondroitin sulphate on CVL.. This post hoc analysis of a clinical trial used the according-to-protocol population (chondroitin sulphate, n = 57; celecoxib, n = 63) baseline and 2-year MRI to assess bone curvature and CVL. Global optimum search identified the BCROI in the medial condyle using celecoxib as reference. Statistical analyses were performed with Pearson's correlation, Mann-Whitney U -test, Student's t -test and analysis of covariance.. The BCROI including the medial posterior condyle and lateral central condyle was found to correlate best with medial condyle CVL at 2 years ( r = 0.33, P = 0.008). In patients with a baseline BCROI value less than the median (more flattened bone), chondroitin sulphate demonstrated a protective effect on CVL compared with celecoxib in the medial compartment (P = 0.037). In patients with 2-year BCROI changes greater than the median (greater severity of bone flattening), chondroitin sulphate protected against CVL in the medial compartment, condyle and central plateau (P ⩽ 0.030).. This study is the first to demonstrate the feasibility and usefulness of bone curvature measurements to predict effectiveness of OA treatment on CVL. The results identify bone curvature as a potential novel biomarker for knee OA clinical trials.

Topics: Adult; Aged; Bone Diseases; Cartilage Diseases; Cartilage, Articular; Celecoxib; Chondroitin Sulfates; Cyclooxygenase 2 Inhibitors; Double-Blind Method; Female; Humans; Male; Middle Aged; Organ Size; Osteoarthritis, Knee

Calcified cartilage is a mineralized osteochondral interface region between the hyaline cartilage and subchondral bone. There are few reported artificial biomaterials that could offer bioactivities for substantial reconstruction of calcified cartilage. Herein we developed new poly(L-lactide-

Topics: Animals; Biocompatible Materials; Bone Diseases; Calcification, Physiologic; Cartilage; Chondroitin Sulfates; Disease Models, Animal; Glass; Membranes, Artificial; Polyesters; Prostheses and Implants; Rabbits; Tensile Strength; X-Ray Microtomography

Bone morphogenetic protein 2 (BMP-2)-loaded collagen sponges remain the clinical standard for treatment of large bone defects when there is insufficient autograft, despite associated complications. Recent efforts to negate comorbidities have included biomaterials and gene therapy approaches to extend the duration of BMP-2 release and activity. In this study, we compared the collagen sponge clinical standard to chondroitin sulfate glycosaminoglycan (CS-GAG) scaffolds as a delivery vehicle for recombinant human BMP-2 (rhBMP-2) and rhBMP-2 expression via human BMP-2 gene inserted into mesenchymal stem cells (BMP-2 MSC). We demonstrated extended release of rhBMP-2 from CS-GAG scaffolds compared to their collagen sponge counterparts, and further extended release from CS-GAG gels seeded with BMP-2 MSC. When used to treat a challenging critically sized femoral defect model in rats, both rhBMP-2 and BMP-2 MSC in CS-GAG induced comparable bone formation to the rhBMP-2 in collagen sponge, as measured by bone volume, strength, and stiffness. We conclude that CS-GAG scaffolds are a promising delivery vehicle for controlling the release of rhBMP-2 and to mediate the repair of critically sized segmental bone defects. Stem Cells Translational Medicine 2019;8:575-585.

Topics: Animals; Bone Diseases; Bone Morphogenetic Protein 2; Bone Regeneration; Chondroitin Sulfates; Collagen; Female; Humans; Hydrogels; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Nanofibers; Rats; Rats, Nude; Recombinant Proteins; Tissue Scaffolds; Transforming Growth Factor beta

Skeletal bone losses are mainly filled with autologous graft or artificial materials. Osteoblasts are essential to maintain bone homeostasis and bone repair through a matrix synthesis. We have previously demonstrated that adherence and regenerative matrix composition are fundamental to bone healing, even in critical situations. In this work the critical size defect technique was used to evaluate the systemic activity on bone regeneration of a novel mixture of extracellular polysaccharides. A 5mm diameter hole was made in each parietal bone of male Wistar rats. The right parietal bone hole was filled with a mixture of hyaluronic acid, chondroitin 6 sulphate, and dermatan sulphate mixed with 2.5% NaCl solution, while the left hole was left free of material and untreated and considered as control. Twenty-one days after surgery, the holes and surrounding tissues were examined visually, using X-rays, and by histological staining. Using the matrix substitute, bone healing was almost complete after 21 days in the treated hole and always complete in the control side due to some systemic effect. Neovascularization was also observed along with organized trabecular bone on both sides. No abnormal bone growth or connective tissue abnormalities were noted. At the end of the experiment, 95.1% (± 3.2) bone healing (n=20) was observed on the treated side; conversely, healing bone and histological structure were better on the control side.

Topics: Animals; Biocompatible Materials; Bone Diseases; Bone Regeneration; Chondroitin Sulfates; Dermatan Sulfate; Disease Models, Animal; Hyaluronic Acid; Male; Neovascularization, Physiologic; Osteogenesis; Parietal Bone; Periosteum; Rats; Rats, Wistar; Time Factors; Wound Healing

In order to investigate the involvement of cartilage proteoglycans in the pathogenesis of human congenital skeletal disorders, proteoglycans were extracted with 4 M guanidine HCl from the iliac crest cartilage of children with various skeletal diseases; lysosomal storage diseases (group I), osteochondrodysplasias (group II) and controls (group III). The cartilage-type proteoglycan (PG-H) was purified and its chondroitin sulfate moiety was analyzed by digestion with chondroitinase-ABC. In group II and group III, the relative amounts of the unsaturated disaccharide products changed in an age-related manner; decrease (from 50% to 30%) of delta Di-4S with a compensatory increase (from 40% to 60%) of delta Di-6S with increasing age from 0 to 15 years. On the other hand, some cases in group I showed aberrant composition of the disaccharide products; a lower content of delta Di-4S with a correspondingly higher content of delta Di-6S. Patients in group I have clinically similar skeletal disorders, and the extent of the compositional abnormality seems to reflect the severity of the skeletal disorder. Therefore, one may consider that the aberrant composition of the glycosaminoglycans in PG-H is involved in the pathogenesis of the skeletal disorder of lysosomal storage diseases.

Topics: Adolescent; Bone Diseases; Cartilage; Child; Child, Preschool; Chondroitin; Chondroitin Sulfates; Chromatography, Gel; Female; Humans; Ilium; Infant, Newborn; Male; Metabolism, Inborn Errors; Proteoglycans

Crude glycosaminoglycan (GAG) fraction was directly precipitated with cetylpyridinium chloride without prior dialysis of urine of orthopedic patients. The crude GAG fraction was then fractionated with trichloroacetic acid (TCA). The TCA-insoluble peptide-bound GAG fraction thus obtained was treated with alkali to eliminate the peptide moiety for enzymatic analysis. The GAG compositions of this fraction and the TCA-soluble fraction were determined by digestion with mucopolysaccharidases (chondroitinase AC, chondroitinase B, chondroitinase C, heparitinase and Streptomyces hyaluronidase). When the amount of the crude GAG fraction was small, no significant amount of the TCA-insoluble peptide-bound GAG fraction was obtained. The GAG composition of this case was also determined by the same procedures after direct alkali-treatment of the crude GAG fraction. The data indicated that the proportion of the TCA-insoluble peptide-bound GAG fraction was very small. The alkali-treated TCA-insoluble peptide-bound GAG fraction contained a larger proportion of heparan sulfate than the TCA-soluble GAG fraction. It was clearly demonstrated that the patients with Werner's syndrome and mucopolysaccharidosis I-S (Scheie) excreted large amounts of hyaluronic acid and dermatan sulfate respectively, into urines. It was indicated in most cases that major urinary GAG were chondroitin 4-sulfate, chondroitin 6-sulfate plus chondroitin and heparan sulfate, while minor ones were dermatan sulfate and hyaluronic acid. In addition, the data suggested a wide range of the degree of desulfation or urinary GAG, and the presence of significant amounts of keratan sulfate plus acidic glycopeptides in the urinary GAG fractions. The present data provided more precise information on urinary GAG from orthopedic patients than those reported previously.

Topics: Adolescent; Adult; Aged; Bone Diseases; Chemical Fractionation; Chondroitin Sulfates; Dermatan Sulfate; Female; Glucuronidase; Glycosaminoglycans; Heparitin Sulfate; Humans; Hyaluronic Acid; Lyases; Male; Middle Aged; Mucopolysaccharidosis I; Werner Syndrome

Glycosaminoglycan peptides prepared by papain hydrolysis of different regions were obtained from osteoarthrotic and normal human femoral heads. Data obtained in these experiments show that in osteoarthrosis a decrease in keratan sulfate and an increase in chondroitin sulfate are observed. Since keratan sulfate appeared to play an important role in proteoglycan aggregation, we suggest that the keratan sulfate decrease is one of the factors involved in the cartilage disorder observed in patients suffering from osteoarthrosis.

Topics: Aged; Bone Diseases; Cartilage, Articular; Chemical Phenomena; Chemistry; Chondroitin Sulfates; Electrophoresis, Agar Gel; Femur; Glycosaminoglycans; Humans; Joint Diseases; Keratan Sulfate; Middle Aged; Peptides; Proteoglycans

Topics: Adolescent; Body Fluids; Bone Diseases; Chondroitin; Chondroitin Sulfates; Dermatan Sulfate; Dysostoses; Humans; Urine