Keratan sulfate

About: Keratan sulfate is a research topic. Over the lifetime, 1253 publications have been published within this topic receiving 57984 citations. The topic is also known as: keratan sulfate & KS.

Degradation of small leucine-rich repeat proteoglycans by matrix metalloprotease-13: identification of a new biglycan cleavage site

Abstract: A major and early feature of cartilage degeneration is proteoglycan breakdown. Matrix metalloprotease (MMP)-13 plays an important role in cartilage degradation in osteoarthritis (OA). This MMP, in addition to initiating collagen fibre cleavage, acts on several proteoglycans. One of the proteoglycan families, termed small leucine-rich proteoglycans (SLRPs), was found to be involved in collagen fibril formation/interaction, with some members playing a role in the OA process. We investigated the ability of MMP-13 to cleave members of two classes of SLRPs: biglycan and decorin; and fibromodulin and lumican. SLRPs were isolated from human normal and OA cartilage using guanidinium chloride (4 mol/l) extraction. Digestion products were examined using Western blotting. The identities of the MMP-13 degradation products of biglycan and decorin (using specific substrates) were determined following electrophoresis and microsequencing. We found that the SLRPs studied were cleaved to differing extents by human MMP-13. Although only minimal cleavage of decorin and lumican was observed, cleavage of fibromodulin and biglycan was extensive, suggesting that both molecules are preferential substrates. In contrast to biglycan, decorin and lumican, which yielded a degradation pattern similar for both normal and OA cartilage, fibromodulin had a higher level of degradation with increased cartilage damage. Microsequencing revealed a novel major cleavage site (... G177/V178) for biglycan and a potential cleavage site for decorin upon exposure to MMP-13. We showed, for the first time, that MMP-13 can degrade members from two classes of the SLRP family, and identified the site at which biglycan is cleaved by MMP-13. MMP-13 induced SLRP degradation may represent an early critical event, which may in turn affect the collagen network by exposing the MMP-13 cleavage site in this macromolecule. Awareness of SLRP degradation products, especially those of biglycan and fibromodulin, may assist in early detection of OA cartilage degradation.

Human endometrial muc1 carries keratan sulfate: characteristic glycoforms in the luminal epithelium at receptivity

Abstract: MUC1 is a high molecular mass, highly glycosylated epithelial apical glycoprotein that has been shown to exhibit both adhesive and anti-adhesive properties. Its expression in human glandular endometrial epithelium is transcriptionally regulated with the highest levels in the mid secretory phase, the "receptive" period during which implantation occurs. We demonstrate that endometrial MUC1 carries highly sulfated lactosaminoglycan chains recognized by monoclonal antibody (Mab) 5D4, and the sialokeratan sulfate epitope recognized by Mab D9B1. These glycans are hormonally regulated in endometrium, and show increased abundance in the secretory phase, but detailed evaluation of their distribution shows important differences. The 5D4 epitope is abundant at the luminal epithelial surface until the implantation phase, when it disappears, first from patches of cells, then altogether. D9B1 binding sites are retained in the luminal epithelium at receptivity. These data show that endometrial MUC1 carries sulfated lactosaminoglycans. They identify the luminal epithelial compartment as a site of unique MUC1 glycosylation and independent regulation. Glycosylation and the negative charge associated with sialo- and sulfoglycans may be important in the regulation of embryo attachment.