Chondrocyte-mediated catabolism of aggrecan: aggrecanase-dependent cleavage induced by interleukin-1 or retinoic acid can be inhibited by glucosamine.

  title={Chondrocyte-mediated catabolism of aggrecan: aggrecanase-dependent cleavage induced by interleukin-1 or retinoic acid can be inhibited by glucosamine.},
  author={John D. Sandy and D C Gamett and Vivian P Thompson and Christie Verscharen},
  journal={The Biochemical journal},
  volume={335 ( Pt 1)},
A rat chondrosarcoma cell line and bovine cartilage explants have been used to study the control of aggrecan degradation by chondrocytes treated with interleukin-1 (IL-1) or retinoic acid (RA). Aggrecan fragment analysis with anti-neo-epitope antibodies suggests that aggrecanase (an as yet unidentified enzyme) is the only aggrecan-degrading proteinase active in these cultures. With rat cells, aggrecanase converts the aggrecan core protein into two major G1-domain-bearing products (60 kDa with a… Expand
Chondrocyte-mediated catabolism of aggrecan: evidence for a glycosylphosphatidylinositol-linked protein in the aggrecanase response to interleukin-1 or retinoic acid.
The inhibitory effects of mannosamine, 2-DFG, and PIPLC in rat cells did not appear to be due to an interference with general biosynthetic activity of the cells as measured by [3H]proline incorporation into secreted proteins, and it is suggested that the aggrecanase response by chondrocytes to IL-1 and RA is dependent on the activity of a GPI-anchored protein on the chondroscopic cell surface. Expand
The intermediates of aggrecanase-dependent cleavage of aggrecan in rat chondrosarcoma cells treated with interleukin-1.
It appears that preferential proteinase cleavage in the CS-rich region is determined by properties inherent in the aggrecan monomer itself, such as preferred peptide sequences for enzyme binding or enhanced accessibility to the core protein at these sites. Expand
The intermediates of aggrecanase-dependent cleavage of aggrecan in rat chondrosarcoma cells treated with interleukin-1
We have examined the abundance and structure of intermediates in the chondrocyte-mediated degradation of aggrecan by aggrecanase(s). Degradation products were identified by Western-blot analysis withExpand
10mM glucosamine prevents activation of proADAMTS5 (aggrecanase-2) in transfected cells by interference with post-translational modification of furin.
The effect of glucosamine on ADAMTS5 (a disintegrin-like and metalloprotease domain with thrombospondin type-1 motifs 5), a major aggrecanase in osteoarthritis, is determined and a potential mechanism underlying the observed effects is investigated. Expand
Expression and Regulation of Aggrecanase in Arthritis: The Role of TGF-β1
Real-time PCR demonstrated that TGF-β significantly increased aggrecanase-1 gene expression in FLS, and aggreCanase-2 protein may be regulated by a post-translational mechanism in OA and RA ST, which can contribute to cartilage degradation in RA and OA. Expand
Effect of glucosamine and chondroitin sulfate on regulation of gene expression of proteolytic enzymes and their inhibitors in interleukin-1-challenged bovine articular cartilage explants.
GLN and CS, at concentrations that are within the range measured in synovial fluid and blood after oral administration, may regulate expression of matrix degrading enzymes and their inhibitors at the transcriptional level, providing a plausible mechanism for their purported chondroprotective properties. Expand
Aggrecanase-mediated cartilage degradation.
  • E. Arner
  • Chemistry, Medicine
  • Current opinion in pharmacology
  • 2002
Additional substrates have now been identified, including the chondroitin-sulfate proteoglycans brevican and versican, which may be upregulated in arthritic synovium at either the message level or through post-translational processing. Expand
Glucosamine sulfate modulates the levels of aggrecan and matrix metalloproteinase-3 synthesized by cultured human osteoarthritis articular chondrocytes.
It is indicated that GS can stimulate mRNA and protein levels of aggrecan core protein and, at the same time, inhibit production and enzymatic activity of matrix-degrading MMP-3 in chondrocytes from OA articular cartilage. Expand
Regulation of aggrecanase-1 and aggrecanase-2 expressions by hypoxia and cytokines in rheumatoid fibroblast-like synoviocytes
It is suggested that hypoxia and cytokines enhance the aggrecanase activity of RA FLS and contribute to joint destruction. Expand
Glucosamine Hydrochloride but Not Chondroitin Sulfate Prevents Cartilage Degradation and Inflammation Induced by Interleukin-1α in Bovine Cartilage Explants
GH prevents cartilage degradation mediated by aggrecanases ADAMTS-4 and -5, and may also reduce inflammation, which could be part of the mechanisms by which GH is effective in maintaining joint integrity and function, and preventing or delaying early symptoms of OA. Expand