Lead inhibits the basal and stimulated responses of a rat osteoblast-like cell line ROS 17/2.8 to 1 alpha,25-dihydroxyvitamin D3 and IGF-I.
Low-level exposure to lead impairs longitudinal growth in children and in experimental animals. The proposed mechanisms include decreased osteocalcin secretion in response to 1 alpha,25-(OH)2 vitamin D3 and decreased response to insulin-like growth factor-I. The interaction of lead, 1 alpha,25-(OH)2 vitamin D3, and insulin-like growth factor-I was investigated in an osteoblast-like cell line from rat osteosarcoma, ROS 17/2.8. Cells were cultured 24 hr in a serum-free medium with lead, 1 alpha,25-(OH)2 vitamin D3, and insulin-like growth factor-I. 1 alpha,25-(OH)2 vitamin D3 (10 nM) evoked a 4-5 X increase in osteocalcin secretion and a 100% increase in cellular alkaline phosphatase activity but no increase in DNA/cell layer. Insulin-like growth factor-I (92.5 ng/ml) evoked a 100% increase of osteocalcin secretion and a 20% increase in cellular DNA contents but no change in cellular alkaline phosphatase activity. Basal and stimulated cellular osteocalcin secretion, cellular alkaline phosphatase activity, and DNA contents were significantly inhibited by addition of 1-10 microM lead. The data are consistent with a toxic effect of lead on osteoblastic function and the cellular responses to 1 alpha,25-(OH)2 vitamin D3 and insulin-like growth factor-I. This interaction may be relevant to impaired childhood growth at low levels of lead exposure.
Angle
C R
CR
Department of Pediatrics, University of Nebraska Medical Center, Omaha 68105-1065.
Thomas
D J
DJ
Swanson
S A
SA
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D002460:Cell Line / Q000187:drug effects; D003470:Culture Media / Q000032:analysis; D004247:DNA / Q000378:metabolism; D004347:Drug Interactions; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007854:Lead / Q000633:toxicity*; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D015675:Osteocalcin / Q000378:metabolism; D051381:Rats; D013002:Somatomedins / Q000494:pharmacology*
D003470:Culture Media; D013002:Somatomedins; D015675:Osteocalcin; D007854:Lead; D007334:Insulin-Like Growth Factor I; D004247:DNA; D000469:Alkaline Phosphatase; D002117:Calcitriol