Inhibition of interleukin 1 beta induced rat and human cartilage degradation in vitro by the metalloproteinase inhibitor U27391
Interleukin 1 induced proteoglycan loss from cartilage in vitro was prevented by a biochemical inhibitor of metalloproteinase activity. The inhibitor also partially relieved the inhibition of proteoglycan synthesis caused by interleukin 1. The loss of glycosaminoglycan by rat and human femoral head...
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Published in | Annals of the rheumatic diseases Vol. 52; no. 1; pp. 37 - 43 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
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London
BMJ Publishing Group Ltd and European League Against Rheumatism
01.01.1993
BMJ BMJ Publishing Group LTD |
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Abstract | Interleukin 1 induced proteoglycan loss from cartilage in vitro was prevented by a biochemical inhibitor of metalloproteinase activity. The inhibitor also partially relieved the inhibition of proteoglycan synthesis caused by interleukin 1. The loss of glycosaminoglycan by rat and human femoral head cartilage in response to human recombinant interleukin 1 beta (rhIL-1 beta) was established, and the modulation of this loss by the metalloproteinase inhibitor U27391 was investigated. Rat femoral head cartilage consistently lost glycosaminoglycan in response to rhIL-1 beta whereas only a proportion (30%) of normal human femoral head cartilage did so. Concentrations of 10-100 mumol/l U27391 inhibited the action of rhIL-1 beta on rat femoral head cartilage, reversing both the loss of glycosaminoglycan and the inhibition of glycosaminoglycan synthesis. U27391 also prevented the reduction in glycosaminoglycan content of those human femoral head cartilage explants responsive to rhIL-1 beta. Metalloproteinase inhibition therefore prevents rhIL-1 beta induced glycosaminoglycan loss by rat and human femoral head cartilage, suggesting that inhibitors of such enzymes may prove to be of therapeutic benefit in erosive diseases in humans. |
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AbstractList | Interleukin 1 induced proteoglycan loss from cartilage in vitro was prevented by a biochemical inhibitor of metalloproteinase activity. The inhibitor also partially relieved the inhibition of proteoglycan synthesis caused by interleukin 1. The loss of glycosaminoglycan by rat and human femoral head cartilage in response to human recombinant interleukin 1 beta (rhIL-1 beta) was established, and the modulation of this loss by the metalloproteinase inhibitor U27391 was investigated. Rat femoral head cartilage consistently lost glycosaminoglycan in response to rhIL-1 beta whereas only a proportion (30%) of normal human femoral head cartilage did so. Concentrations of 10-100 mumol/l U27391 inhibited the action of rhIL-1 beta on rat femoral head cartilage, reversing both the loss of glycosaminoglycan and the inhibition of glycosaminoglycan synthesis. U27391 also prevented the reduction in glycosaminoglycan content of those human femoral head cartilage explants responsive to rhIL-1 beta. Metalloproteinase inhibition therefore prevents rhIL-1 beta induced glycosaminoglycan loss by rat and human femoral head cartilage, suggesting that inhibitors of such enzymes may prove to be of therapeutic benefit in erosive diseases in humans. |
Author | Atkins, R M Seed, M P Ismaiel, S Gardner, C R Thomson, T A Elson, C J Cheung, C Y |
AuthorAffiliation | Roussel Laboratories Ltd., Swindon, Wiltshire, United Kingdom |
AuthorAffiliation_xml | – name: Roussel Laboratories Ltd., Swindon, Wiltshire, United Kingdom |
Author_xml | – sequence: 1 givenname: M P surname: Seed fullname: Seed, M P – sequence: 2 givenname: S surname: Ismaiel fullname: Ismaiel, S – sequence: 3 givenname: C Y surname: Cheung fullname: Cheung, C Y – sequence: 4 givenname: T A surname: Thomson fullname: Thomson, T A – sequence: 5 givenname: C R surname: Gardner fullname: Gardner, C R – sequence: 6 givenname: R M surname: Atkins fullname: Atkins, R M – sequence: 7 givenname: C J surname: Elson fullname: Elson, C J |
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Keywords | Human Biodegradation Rat Enzyme Rodentia Enzyme inhibitor Interleukin 1β Pharmacology In vitro Biological activity Cartilage Vertebrata Mammalia Articular cartilage Animal Metalloproteinase Skeleton |
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SubjectTerms | Animals Biological and medical sciences Bones, joints and connective tissue. Antiinflammatory agents Cartilage, Articular - drug effects Cartilage, Articular - metabolism Culture Techniques Femur Head - metabolism Glycosaminoglycans - metabolism Humans Hydroxamic Acids - pharmacology Interleukin-1 - antagonists & inhibitors Interleukin-1 - pharmacology Interleukin-1 - physiology Male Medical sciences Metalloendopeptidases - antagonists & inhibitors Oligopeptides - pharmacology Pharmacology. Drug treatments Rats Rats, Wistar Recombinant Proteins - pharmacology Sulfates - metabolism |
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Title | Inhibition of interleukin 1 beta induced rat and human cartilage degradation in vitro by the metalloproteinase inhibitor U27391 |
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