Experimental siderosis of articular chondrocytes cultured in vitro.
Siderosis of rabbit articular chondrocytes was produced in vitro as a model for the cartilage damage of hemophilic arthropathy. Both FeSO4 0.1-2.5 mM and rabbit hemoglobin (as hemolyzed serum, 14 mg/ml) caused iron storage in cell and organ culture. FeSO4 was far more effective. The fine structure of the siderosomes resulting from both iron sources was comparable to that observed in hemophilic and other forms of hemosiderosis. Particles resembling ferric oxyhydroxide were included in the FeSO4 but not the hemoglobin derived siderin. Iron storage following FeSO4 was enhanced 5-fold by culturing with rabbit rather than fetal calf serum. Despite repeated washing of the cultures and detachment with trypsin, an extracellular pool of Fe3+ persisted in the cell pellets. Cytotoxicity of Fe was manifested by formation of myelin bodies and a dose-dependent reduction of cell number. There was an inverse relationship between cytotoxicity and iron storage following administration of FeSO4 to five other cell types. Ascorbate 40 micrograms/ml stimulated DNA synthesis but had no protective effect against the cytotoxicity of FeSO4. Little erythrophagocytosis was showen by the chondrocytes. Desferrioxamine (0.01--2.5 mM) was markedly toxic for dividing but not for stationary chondrocytes. Administered after iron storage had been induced with FeSO4, 1.0--2.5 mM desferrioxamine removed stainable siderin granules over the course of 4 days.
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D002358:Cartilage, Articular / Q000166:cytology* / Q000187:drug effects; D002417:Cattle; D002478:Cells, Cultured; D003676:Deferoxamine / Q000494:pharmacology; D004195:Disease Models, Animal; D004912:Erythrocytes / Q000276:immunology; D005296:Ferrous Compounds / Q000494:pharmacology; D007501:Iron / Q000378:metabolism; D009924:Organ Culture Techniques; D010586:Phagocytes / Q000276:immunology; D011817:Rabbits; D012806:Siderosis / Q000473:pathology*
D005296:Ferrous Compounds; C020748:ferrous sulfate; D007501:Iron; D003676:Deferoxamine; D001205:Ascorbic Acid