Lead impairs the production of osteocalcin by rat osteosarcoma (ROS 17/2.8) cells
G J Long1, J F Rosen, J G Pounds
1Department of Applied Science, Brookhaven National Laboratory, Upton, New York 11973.
Abstract:
The serum level of osteocalcin, a bone-specific protein produced by osteoblasts and an index of bone formation, is decreased in lead-intoxicated children. To elucidate the effect of lead on the hormonal regulation of osteocalcin production, ROS 17/2.8 cells were treated with 0, 5, 10, or 25 microM lead acetate for 24 hr, followed by an additional 24-hr lead treatment with or without 100 pg 1,25-dihydroxyvitamin D3/ml medium. At the end of this period a radioimmunoassay was conducted to determine the amount of osteocalcin present in the cells and secreted into the medium. 1,25-Dihydroxyvitamin D3 increased osteocalcin secretion in control cultures, but this increase was prevented by lead in a concentration-dependent manner. Osteocalcin secretion by cultures treated with 10 or 25 microM lead was even lower than in cultures not stimulated with 1,25-dihydroxyvitamin D3. Intracellular levels of osteocalcin were slightly elevated with 1,25-dihydroxyvitamin D3, and there was no lead effect on cellular levels. These data indicate that lead attenuates basal and 1,25-dihydroxyvitamin D3-stimulated production of osteocalcin in ROS 17/2.8 cells. Because osteocalcin appears to play a central role in bone mineralization, altered osteocalcin production may be a key event in the skeletal toxicity of lead.
Insights
Lead exposure in children lowers osteocalcin, a key bone formation protein. This study shows lead acetate in cell cultures inhibits vitamin D
Area of Science:
- Biochemistry
- Toxicology
- Endocrinology
Background:
- Osteocalcin is a crucial bone-specific protein indicating bone formation.
- Lead intoxication in children is linked to decreased serum osteocalcin levels.
- The precise mechanism of lead's effect on osteocalcin regulation is not fully understood.
Purpose of the Study:
- To investigate the impact of lead on the hormonal regulation of osteocalcin production.
- To determine if lead interferes with vitamin D's effect on osteocalcin.
Main Methods:
- ROS 17/2.8 cells were treated with varying concentrations of lead acetate.
- Cells were subsequently treated with or without 1,25-dihydroxyvitamin D3.
- Osteocalcin levels (intracellular and secreted) were measured using radioimmunoassay.
Main Results:
- 1,25-dihydroxyvitamin D3 stimulated osteocalcin secretion in control cells.
- Lead acetate inhibited this vitamin D-stimulated osteocalcin secretion in a dose-dependent manner.
- Lead exposure reduced osteocalcin secretion below basal levels, without affecting intracellular osteocalcin.
Conclusions:
- Lead exposure attenuates both basal and vitamin D-stimulated osteocalcin production in bone cells.
- This disruption of osteocalcin production may contribute to lead's skeletal toxicity.
- Altered osteocalcin levels due to lead could impair bone mineralization.
