title: Induction of metalloproteinase activity, cartilage matrix degradation and inhibition of endochondral mineralization in vitro by E. coli lipopolysaccharide is mediated by interleukin 1 alpha.
abstract: Chronic inflammation and degradation of connective tissue in the course of periodontitis are maintained by bacterial products such as lipopolysaccharides (LPS), which probably act via inflammation mediators, e.g. cytokines. We investigated the effects of lipopolysaccharide (LPS) from E. coli and mouse recombinant interleukin 1 alpha (mrIL-1) on chondrogenesis, endochondral mineralization, matrix metalloproteinase activation and matrix degradation in vitro using cartilage organoid cultures. Mesenchymal cells of limb buds from mouse embryos (day 12) were grown at high density on a membrane filter at the medium/air interphase for 14 days. Chondrogenesis occurred during the first 6 days of culture. Endochondral mineralization took place upon addition of 5 mM beta-glycerophosphate from day 7 to 14. Treatment of the cultures with LPS and mrIL-1 on days 2 to 14 and during mineralization on days 7 to 14 resulted in a marked decrease of types I and II collagen, matrix mineralization and proteoglycan content. In the medium, proteoglycan content and metalloproteinase activity were enhanced. LPS induced IL-1 alpha production and release into the medium. LPS antagonist polymyxin B partly abolished the LPS effect, whereas IL-1 receptor antagonist (IL-1ra) partly abolished both LPS and mrIL-1 effects. Reversal of LPS-induced effects by IL-1ra was comparable to the reversal of mrIL-1 effects, only the decrease in type II collagen after LPS treatment was abolished to a lesser extent by IL-1ra.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Institute of Toxicology and Prenatal Pharmacology, Free University of Berlin, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Scheller
authors.forename: B
authors.initials: B
authors.lastname: Zimmermann
authors.forename: J P
authors.initials: JP
authors.lastname: Bernimoulin
authors.forename: P
authors.initials: P
authors.lastname: Scholz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002114:Calcinosis / Q000503:physiopathology*; D002358:Cartilage, Articular / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D004731:Endotoxins / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects; D005109:Extracellular Matrix / Q000378:metabolism*; D005994:Glycerophosphates / Q000494:pharmacology; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D008648:Mesoderm; D008666:Metalloendopeptidases / Q000096:biosynthesis*; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009924:Organ Culture Techniques; D009940:Organoids; D011112:Polymyxin B / Q000494:pharmacology; D011509:Proteoglycans / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000494:pharmacology
chemical_list: D004731:Endotoxins; D005994:Glycerophosphates; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D011509:Proteoglycans; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; C044101:endotoxin, Escherichia coli; D003094:Collagen; D008666:Metalloendopeptidases; D011112:Polymyxin B; C031463:beta-glycerophosphoric acid