Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.6.4 (chondroitinase)
 2,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Collagen content and tensile properties of engineered articular cartilage have remained inferior to glycosaminoglycan (GAG) content and compressive properties. Based on a cartilage explant study showing greater tensile properties after chondroitinase ABC (C-ABC) treatment, C-ABC as a strategy for cartilage tissue engineering was investigated. A scaffold-less approach was employed, wherein chondrocytes were seeded into non-adherent agarose molds. C-ABC was used to deplete GAG from constructs 2 weeks after initiating culture, followed by 2 weeks culture post-treatment. Staining for GAG and type I, II, and VI collagen and transmission electron microscopy were performed. Additionally, quantitative total collagen, type I and II collagen, and sulfated GAG content were measured, and compressive and tensile mechanical properties were evaluated. At 4 wks, C-ABC treated construct ultimate tensile strength and tensile modulus increased 121% and 80% compared to untreated controls, reaching 0.5 and 1.3 MPa, respectively. These increases were accompanied by increased type II collagen concentration, without type I collagen. As GAG returned, compressive stiffness of C-ABC treated constructs recovered to be greater than 2 wk controls. C-ABC represents a novel method for engineering functional articular cartilage by departing from conventional anabolic approaches. These results may be applicable to other GAG-producing tissues functioning in a tensile capacity, such as the musculoskeletal fibrocartilages.
 ...
PMID:Chondroitinase ABC treatment results in greater tensile properties of self-assembled tissue-engineered articular cartilage. 1934 91

Dermatan sulfate (DS) expression in normal tissue and ovarian cancer was investigated using the novel, phage display-derived antibody GD3A12 that was selected against embryonic glycosaminoglycans (GAGs). Antibody GD3A12 was especially reactive with DS rich in IdoA-GalNAc4S disaccharide units. IdoA residues are important for antibody recognition as DS polymers with low numbers of IdoA residues were less reactive, and expression of the DS epimerase in ovarian carcinoma cells was associated with expression of the GD3A12 epitope. Moreover, staining of antibody GD3A12 was abolished by chondroitinase-B lyase digestion. Expression of DS domains defined by antibody GD3A12 was confined to connective tissue of most organs examined and presented as a typical fibrillar-type of staining. Differential expression of the DS epitopes recognized by antibodies GD3A12 and LKN1 (4/2,4 di-O-sulfated DS) was best seen in thymus and spleen, indicating differential expression of various DS domains in these organs. In ovarian carcinomas strong DS expression was found in the stromal parts, and occasionally on tumor cells. Partial co-localization in ovarian carcinomas was observed with decorin, versican and type I collagen suggesting a uniform distribution of this specific DS epitope. This unique anti-DS antibody may be instrumental to investigate the function, expression, and localization of specific DS domains in health and disease.
 ...
PMID:Dermatan sulfate domains defined by the novel antibody GD3A12, in normal tissues and ovarian adenocarcinomas. 1936 Apr 34

The amniotic membrane (AM) is the innermost layer of fetal membranes and possesses various biological activities. Although the mechanism underlying these biological activities remains unclear, unique components seem to be involved. AM contains various extracellular matrix components such as type I collagen, laminin, fibronectin, hyaluronan, and proteoglycans bearing chondroitin sulfate/dermatan sulfate (CS/DS) glycosaminoglycan side chains. Since CS/DS have been implicated in various biological processes, we hypothesized that CS/DS in AM may play a major role in the biological activities of AM. Therefore, the structure and bioactivity of the CS/DS chains from porcine fetal membranes (FM-CS/DS) were investigated. A compositional analysis using various chondroitinases revealed that the characteristic DS domain comprised of iduronic acid-containing disaccharide units is embedded in FM-CS/DS, along with predominant disaccharide units, GlcA-GalNAc, GlcA-GalNAc(4-O-sulfate), and GlcA-GalNAc(6-O-sulfate), where GlcA and GalNAc represent D-glucuronic acid and N-acetyl-D-galactosamine, respectively. The average molecular mass of FM-CS/DS chains was unusually large and estimated to be 250 - 300 kDa. The FM-CS/DS chains showed neurite outgrowth-promoting activity, which was eliminated by digestion with chondroitinase ABC of the CS/DS chains. This activity was suppressed by antibodies against growth factors including pleiotrophin, midkine, and fibroblast growth factor-2, suggesting the involvement of these growth factors in the neurite outgrowth-promoting activity. The binding of these growth factors to FM-CS/DS was also demonstrated by surface plasmon resonance spectroscopy.
 ...
PMID:Analysis of the structure and neuritogenic activity of chondroitin sulfate/dermatan sulfate hybrid chains from porcine fetal membranes. 1980 51

A multifaceted therapeutic approach involving biomaterial scaffolds, neurotrophic factors, exogenous cells, and antagonists to axon growth inhibitors may ultimately prove necessary for the treatment of defects resulting from spinal cord injury (SCI). The objective of this study was to begin to lay the groundwork for such strategies by implanting type I collagen scaffolds alone and incorporating individually a soluble Nogo receptor, chondroitinase ABC (ChABC), and mesenchymal stem cells (MSCs) into a standardized 3-mm-long hemiresection defect in the rat spinal cord. Statistically significant improvement in hindlimb motor function between the first and fourth weeks post-SCI was recorded for the scaffold-alone group and for the ChABC and MSC groups, but not the control group. Four weeks post-SCI, the scaffolds appeared intact with open pores, which were infiltrated with host cells. Of note is that in some cases, a few growth-associated protein 43 (GAP-43)-positive axons were seen reaching the center of the scaffold in the scaffold-alone and ChABC groups, but not in control animals. Angiogenic cells were prevalent in the scaffolds; however, the number of both macrophages and angiogenic cells in the scaffolds was significantly less than in the control lesion at 4 weeks. The results lay the foundation for future dose-response studies and to further investigate a range of therapeutic agents to enhance the regenerative response in SCI.
 ...
PMID:Collagen scaffolds incorporating select therapeutic agents to facilitate a reparative response in a standardized hemiresection defect in the rat spinal cord. 2282 32

Collagen crosslinking is a relatively new treatment for structural disorders of corneal ectasia, such as keratoconus. However, there is a lack of animal models of keratoconus, which has been an obstacle for carefully analyzing the mechanisms of crosslinking and evaluating new therapies. In this study, we treated rabbit eyes with collagenase and chondroitinase enzymes to generate ex vivo corneal ectatic models that simulate the structural disorder of keratoconus. The models were then used to evaluate the protective effect of soluble collagen in the UVA crosslinking system. After enzyme treatment, the eyes were exposed to riboflavin/UVA crosslinking with and without soluble type I collagen. Corneal morphology, collagen ultrastructure, and thermal stability were evaluated before and after crosslinking. Enzyme treatments resulted in corneal curvature changes, collagen ultrastructural damage, decreased swelling resistance and thermal stability, which are similar to what is observed in keratoconus eyes. UVA crosslinking restored swelling resistance and thermal stability, but ultrastructural damage were found in the crosslinked ectatic corneas. Adding soluble collagen during crosslinking provided ultrastructural protection and further enhanced the swelling resistance. Therefore, UVA crosslinking on the ectatic model mimicked typical clinical treatment for keratoconus, suggesting that this model replicates aspects of human keratoconus and could be used for investigating experimental therapies and treatments prior to translation.
...
PMID:Protective Effects of Soluble Collagen during Ultraviolet-A Crosslinking on Enzyme-Mediated Corneal Ectatic Models. 2632 7


<< Previous 1 2 3