Lead impairs the production of osteocalcin by rat osteosarcoma (ROS 17/2.8) cells.
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.
Long
G J
GJ
Department of Applied Science, Brookhaven National Laboratory, Upton, New York 11973.
Rosen
J F
JF
Pounds
J G
JG
D000818:Animals; D002117:Calcitriol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007854:Lead / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D007855:Lead Poisoning / Q000378:metabolism; D015675:Osteocalcin / Q000096:biosynthesis* / Q000378:metabolism; D012516:Osteosarcoma / Q000378:metabolism* / Q000473:pathology; D011863:Radioimmunoassay; D051381:Rats; D013997:Time Factors; D014407:Tumor Cells, Cultured
D015675:Osteocalcin; D007854:Lead; D002117:Calcitriol