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Inhibition of cartilage proteoglycan release by a specific inactivator of cathepsin B and an inhibitor of matrix metalloproteinases. Evidence for two converging pathways of chondrocyte-mediated proteoglycan degradation.
- Source :
-
Arthritis and rheumatism [Arthritis Rheum] 1993 Dec; Vol. 36 (12), pp. 1709-17. - Publication Year :
- 1993
-
Abstract
- Objective: To investigate mechanisms of cartilage matrix destruction by a study of the effects of a specific inactivator of cathepsin B and an inhibitor of several matrix metalloproteinases (MMP) on cartilage proteoglycan release.<br />Methods: Cartilage explants were treated with either recombinant human interleukin-1 alpha (rHuIL-1 alpha) or retinoic acid in the presence or absence of the inhibitors, and proteoglycan release was quantitated. Tests for nonspecific effects of the inhibitors included reversibility, rates of protein synthesis and glycolysis, and effects on other rHuIL-1 alpha-mediated events.<br />Results: The cathepsin B inactivator inhibited rHuIL-1 alpha-stimulated proteoglycan release at nanomolar concentrations, but failed to significantly inhibit retinoic acid-stimulated proteoglycan release. An inhibitor of MMP was inhibitory to both rHuIL-1 alpha-stimulated release and retinoic acid-stimulated release.<br />Conclusion: Cathepsin B is implicated in rHuIL-1 alpha-stimulated loss of cartilage proteoglycan. Its lack of involvement in retinoic acid-stimulated proteoglycan release suggests the existence of at least 2 pathways of cartilage proteoglycan breakdown, which may converge at the activation of a matrix prometalloproteinase.
- Subjects :
- Aggrecans
Amino Acid Sequence
Animals
Cartilage enzymology
Cartilage, Articular enzymology
Cattle
Dipeptides pharmacology
Enzyme Activation
Interleukin-1 pharmacology
Lectins, C-Type
Molecular Sequence Data
Nasal Septum chemistry
Nasal Septum drug effects
Nasal Septum metabolism
Peptide Fragments chemistry
Phenylalanine analogs & derivatives
Phenylalanine pharmacology
Proteoglycans chemistry
Proteoglycans drug effects
Recombinant Proteins pharmacology
Thiophenes pharmacology
Tretinoin pharmacology
Cartilage chemistry
Cathepsin B antagonists & inhibitors
Extracellular Matrix Proteins
Metalloendopeptidases antagonists & inhibitors
Proteoglycans metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0004-3591
- Volume :
- 36
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Arthritis and rheumatism
- Publication Type :
- Academic Journal
- Accession number :
- 8250991
- Full Text :
- https://doi.org/10.1002/art.1780361210