Inhibition of cell differentiation by manganese chloride in micromass cultures of mouse embryonic limb bud cells

Although manganese is an essential element, in excess it has proven to be toxic to a number of organ systems. In several studies, exposure to manganese compounds during embryological development has been linked to skeletal abnormalities. Micromass cultures of dissociated mouse embryonic limb bud cells were used to investigate whether manganese could interfere with the process of chondrogenesis. Cell viability was significantly reduced in cultures grown in the presence of 1 and 10 mm MnCl2, whereas as little as 10 mum MnCl2 inhibited differentiation of limb cells into proteoglycan-producing nodules. Because the concentration of MnCl2 needed to interfere with differentiation is so much lower than the cytotoxic concentration, it is suggested that manganese has the potential to be teratogenic, and to specifically interfere with the development of a cartilage matrix, although by an unknown mechanism. (C) 2002 Elsevier Science Ltd. All rights reserved.