EFFECTS OF LEAD ON GROWTH-PLATE CHONDROCYTE PHENOTYPE

Lead toxicity is a major public health problem in the United States. T he skeleton serves as the major reservoir for ingested lead, where it is incorporated into bone matrix during calcification. While lead in b one has been considered inactive, mounting clinical and epidemiologica l data has shown a strong correlation between lead exposure and advers e effects on stature in children, These epidemiologic data suggest a d irect effect of lead on skeletal development, but whether it reflects a systemic effect, a specific effect on osteoblasts, or an effect on t he epiphyseal growth plate is as yet unclear. This study examined the effects of lead on parameters of cartilage biology in isolated chondro cytes. Changes in growth plate chondrocyte phenotype were assessed uti lizing an established avian growth plate chondrocyte model. Low, suble thal doses of lead caused specific and significant effects on a number of important markers of growth plate chondrocyte phenotype, including suppression of alkaline phosphatase and both type II and type X colla gen expression at the protein and mRNA levels, and a decrease in thymi dine incorporation. In contrast, proteoglycan synthesis was stimulated relative to controls in lead-treated cultures, suggesting that the al terations in collagen and DNA synthesis and alkaline phosphatase activ ity are not due to cytotoxity. The data demonstrate important regulato ry effects of lead on growth plate chondrocytes in cell culture and su ggest an inhibitory effect on the process of endochondral bone formati on. The growth plate may be one of the key target tissues accounting f or the adverse effects of chronic lead exposure on skeletal developmen t. (C) 1996 Academic Press, Inc.