Effects of lead on growth plate chondrocyte phenotype.
Lead toxicity is a major public health problem in the United States. The skeleton serves as the major reservoir for ingested lead, where it is incorporated into bone matrix during calcification. While lead in bone has been considered inactive, mounting clinical and epidemiological data has shown a strong correlation between lead exposure and adverse effects on stature in children. These epidemiologic data suggest a direct effect of lead on skeletal development, but whether it reflects a systemic effect, a specific effect on osteoblasts, or an effect on the epiphyseal growth plate is as yet unclear. This study examined the effects of lead on parameters of cartilage biology in isolated chondrocytes. Changes in growth plate chondrocyte phenotype were assessed utilizing an established avian growth plate chondrocyte model. Low, sublethal 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 collagen expression at the protein and mRNA levels, and a decrease in thymidine incorporation. In contrast, proteoglycan synthesis was stimulated relative to controls in lead-treated cultures, suggesting that the alterations in collagen and DNA synthesis and alkaline phosphatase activity are not due to cytotoxity. The data demonstrate important regulatory effects of lead on growth plate chondrocytes in cell culture and suggest an inhibitory effect on the process of endochondral bone formation. The growth plate may be one of the key target tissues accounting for the adverse effects of chronic lead exposure on skeletal development.
Hicks
D G
DG
Department of Orthopaedics, University of Rochester School of Medicine, New York 14642, USA.
O'Keefe
R J
RJ
Reynolds
K J
KJ
Cory-Slechta
D A
DA
Puzas
J E
JE
Judkins
A
A
Rosier
R N
RN
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002645:Chickens; D003094:Collagen / Q000096:biosynthesis; D006132:Growth Plate / Q000187:drug effects* / Q000378:metabolism; D017403:In Situ Hybridization; D007854:Lead / Q000633:toxicity*; D010641:Phenotype; D011509:Proteoglycans / Q000096:biosynthesis; D013936:Thymidine / Q000378:metabolism
D011509:Proteoglycans; D007854:Lead; D003094:Collagen; D013936:Thymidine