title: Ciprofloxacin causes cytoskeletal changes and detachment of human and rat chondrocytes in vitro.
abstract: Quinolones cause damage of articular cartilage in different species by forming chelate complexes with divalent cations and inducing magnesium deficiency. Cations are important for regular function of integrins, a group of transmembrane proteins which connect extracellular matrix proteins with the intracellular cytoskeleton. We have shown that cultivation of rat chondrocytes in ciprofloxacin (CFX)-supplemented and Mg(2+)-free medium led to pronounced changes in the cytoskeleton and decreased adhesion of cells to the culture dish. In order to test whether or not these effects are species-specific, we extended our studies on human chondrocytes. Human chondrocytes cultivated in CFX-supplemented medium (10, 40, 80 and 160 microg/ml) or Mg(2+)-free medium showed decreased ability to adhere to growth support, cell shape changes, and alterations in actin and vimentin cytoskeleton in a concentration dependent manner. Attachment of human chondrocytes to collagen type II coated cover slips was reduced to 90% in CFX group and 75% in Mg(2+)-free group on day 1. This effect even increased after 4 days of culture in the respective medium (32% in CFX and 58% in Mg(2+)-free group). We concluded that Mg(2+) deficiency is exerted via integrins, resulting in decreased ability to attach to extracellular matrix proteins and cytoskeletal changes. These effects are not species-specific. The attachment assay proves to be an easy to use experimental set-up to test ciprofloxacin and other quinolones for their chondrotoxic effects.
authors.affiliation: IV Medizinische Abteilung mit Infektions- und Tropenkrankheiten, Kaiser Franz Josef Spital, Kundratstrasse, 1100 Wien, Austria. monika.egerbacher@vu-wien.ac.at
authors.forename: M
authors.initials: M
authors.lastname: Egerbacher
authors.forename: G
authors.initials: G
authors.lastname: Seiberl
authors.forename: B
authors.initials: B
authors.lastname: Wolfesberger
authors.forename: I
authors.initials: I
authors.lastname: Walter
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D002448:Cell Adhesion / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects* / Q000502:physiology; D002939:Ciprofloxacin / Q000494:pharmacology*; D003094:Collagen / Q000494:pharmacology; D003470:Culture Media; D003599:Cytoskeleton / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008274:Magnesium / Q000494:pharmacology; D018613:Microscopy, Confocal; D051381:Rats; D013045:Species Specificity
chemical_list: D000890:Anti-Infective Agents; D003470:Culture Media; D002939:Ciprofloxacin; D003094:Collagen; D008274:Magnesium