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Published on: December 3, 2016
Effects of lead on growth plate chondrocyte phenotype
D G Hicks1, R J O'Keefe, K J Reynolds
1Department of Orthopaedics, University of Rochester School of Medicine, New York 14642, USA.
Insights
Lead exposure negatively impacts children's stature by affecting growth plate chondrocytes. This study reveals low lead doses disrupt collagen synthesis and cell proliferation, indicating a key mechanism for lead-induced skeletal development issues.
Area of Science:
- Skeletal Biology
- Environmental Health
- Toxicology
Background:
- Lead toxicity is a significant public health concern in the U.S.
- The skeleton is the primary reservoir for ingested lead.
- Epidemiological data link lead exposure to adverse effects on children's stature.
Purpose of the Study:
- To investigate the effects of lead on cartilage biology in isolated chondrocytes.
- To assess changes in growth plate chondrocyte phenotype using an avian model.
- To determine if lead directly impacts skeletal development at the cellular level.
Main Methods:
- Isolated avian growth plate chondrocytes were cultured.
- Cells were treated with low, sublethal doses of lead.
- Key markers of chondrocyte phenotype, including alkaline phosphatase, collagen expression (type II and X), and thymidine incorporation, were assessed at the protein and mRNA levels.
- Proteoglycan synthesis was also measured.
Main Results:
- Lead exposure significantly suppressed alkaline phosphatase and collagen types II and X expression.
- Thymidine incorporation, a marker of cell proliferation, decreased in lead-treated cells.
- Proteoglycan synthesis was paradoxically stimulated, suggesting effects beyond general cytotoxicity.
- These findings indicate lead directly regulates growth plate chondrocytes.
Conclusions:
- Lead exposure exerts regulatory effects on growth plate chondrocytes in vitro.
- Lead exposure inhibits endochondral bone formation, a critical process for skeletal development.
- The growth plate is identified as a potential key target tissue responsible for lead's adverse effects on skeletal development in children.
Abstract:
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.
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