Alterations in chondrocyte morphology, proliferation and binding of 35SO4 due to Fe(III), Fe(II), ferritin and haemoglobin in vitro

Lapine articular chondrocytes in vitro were used to study the effects of Fe3+, Fe2+, ferritin and haemoglobin on cell proliferation, synthesis of proteoglycans and morphological structure. Fe3+ (10, 100 and 500 micrograms/ml) reduced the DNA content of cultures by approximately 35% as well as inhibiting proteoglycan synthesis. Chondrocytes showed positive cytoplasmic staining for both ferric and ferrous ions at the 500 micrograms/ml concentration. Fe2+ (100 micrograms/ml) also decreased DNA content and proteoglycan synthesis, although no iron uptake by the chondrocytes could be detected. Ferritin (1.0, 0.5 and 0.1 micrograms/ml) elicited a significant inhibition of proteoglycan synthesis without affecting cellular DNA synthesis. 1 and 5 micrograms/ml of haemoglobin each reduced the DNA content of cultures by 60%, whilst markedly inhibiting proteoglycan synthesis (75 and 99% respectively). None of the substances tested caused chondrocyte toxicity. The ability of Fe3+, Fe2+, ferritin and, in particular, haemoglobin to inhibit chondrocyte proteoglycan synthesis may represent a pathway whereby cartilage is susceptible to destruction in the haemophilic joint.