Disease relevance of AGC1

• The release of aggrecan catabolites from cartilage is an early event in the pathogenesis of degenerative joint diseases [1].
• Transcription of type II collagen, prolyl 4-hydroxylase (alpha subunit), and aggrecan increased in response to the antiscorbutic forms of ascorbic acid (L-Asc, Na L-Asc, and A2P) and was stereospecific to the L-forms [2].

High impact information on AGC1

• To resolve the cartilage proteins by two-dimensional electrophoresis, it was necessary to remove the proteoglycan aggrecan by precipitation with cetylpyridinium chloride [3].
• Generation and novel distribution of matrix metalloproteinase-derived aggrecan fragments in porcine cartilage explants [4].
• Accordingly, the level of aggrecan monomer remaining in the tissue decreased after T(3) treatment, and the monomer lost hyaluronic acid-binding capacity, suggesting that the cleavage site is in the interglobular domain [5].
• These findings suggest that aggrecanse-2/ADAM-TS5 is involved in aggrecan breakdown during endochondral ossification, and that thyroid hormone stimulates the aggrecan breakdown partly via the enhancement of aggrecanase-2/ADAM-TS5 [5].
• These studies show that Fn-f 45 can induce a catabolic phenotype in articular chondrocytes by up-regulating the expression of metalloproteinases specific for the degradation of collagen and aggrecan [6].

Biological context of AGC1

• The keratan sulfate domain of aggrecan consists of a series of tandemly repeating hexapeptides which have the consensus sequence Glu-Glu/Lys-Pro-Phe-Pro-Ser, where the serine side-chains presumably provide sites for the attachment of keratan sulfate (KS) chains [7].
• The hyaluronan-binding region (HABR) was prepared from pig laryngeal cartilage aggrecan and the amino acid sequence was determined [8].
• Anulus fibrosus cells responded to mechanical deformation at the 30-h time point, with increasing gene expression for types I and II collagen, aggrecan, biglycan, decorin and lumican [9].

Anatomical context of AGC1

• Age-related changes in the content of the C-terminal region of aggrecan in human articular cartilage [10].
• Hyaluronan-binding region of aggrecan from pig laryngeal cartilage. Amino acid sequence, analysis of N-linked oligosaccharides and location of the keratan sulphate [11].
• The biochemical significance of these interactions might be more critical in aged vertebrate cartilage, where loss of aggrecan and increase of the small proteoglycans was observed, a large proportion of which is found in the extracellular matrix free of glycosaminoglycan chains [12].
• STUDY DESIGN: The mRNA levels of aggrecan and collagen were quantified in intervertebral disc cells cultured under three conditions: primary alginate culture, monolayer culture, and re-encapsulation in alginate after monolayer culture [13].

Associations of AGC1 with chemical compounds

• Length variation in the keratan sulfate domain of mammalian aggrecan [7].
• Comparison of the structure of the KS chain from the HABR and from the KS domain of pig laryngeal cartilage aggrecan was made by separation on polyacrylamide gels of the oligosaccharides arising from digestion with keratanase [8].
• This study confirms that ascorbic acid stimulates collagen synthesis and in addition modestly stimulates aggrecan synthesis [2].
• We now report that DIPEN(341) neoepitope can be generated post-culture, by dialysing GuHCl(1)-denatured samples against unbuffered, deionized water at 4 degrees C. We show that EDTA must be included in the GuHCl extractant, as well as the dialysis buffer, in order to block post-culture processing of aggrecan by MMPs [14].
• METHOD: An explant culture system was used to investigate the release of the G1 domain of aggrecan from porcine articular cartilage treated with retinoic acid or interleukin 1beta and to study how the activity of these agents is modified by the proteinase inhibitor, batimastat (BB94) [15].

Regulatory relationships of AGC1

• The 45 kDa collagen-binding fragment of fibronectin induces matrix metalloproteinase-13 synthesis by chondrocytes and aggrecan degradation by aggrecanases [6].

Other interactions of AGC1

• Collagen types I and II, aggrecan, and MMP-13 expression was assayed by semiquantitative RT-PCR [16].
• Expression of aggrecan, COMP, decorin, and Col10a1 increased significantly within 52 weeks [17].
• Following either static or dynamic compression, mRNA levels for aggrecan, biglycan and cytoskeletal proteins were unchanged [18].
• The monoclonal antibody (mAb), 5D5, specifically recognizes core proteins of large chondroitin sulphate proteoglycans such as versican, neurocan and brevican, but not the core protein of aggrecan [19].

Analytical, diagnostic and therapeutic context of AGC1

• We used polymerase chain reaction (PCR) to amplify the portion of the human, canine and porcine aggrecan gene that codes for the KS domain [7].
• We have used progressive chondroitinase digestion of pig aggrecan in conjunction with ELISA assays and disaccharide analysis to derive information about the pattern of 4- and 6-sulphation in chondroitin sulphate chains [20].
• Immunohistochemistry showed aggrecan increasing in amount inferiorly [21].

References