title: Stimulatory effect of zinc on deoxyribonucleic acid synthesis in bone growth of newborn rats: enhancement with zinc and insulin-like growth factor-I.
abstract: The effect of zinc on in vitro deoxyribonucleic acid (DNA) synthesis activity in the femoral-diaphyseal and metaphyseal tissues of newborn rats was investigated to determine a role of zinc in bone growth. In vitro DNA synthesis was assayed in a reaction mixture containing the 100 g centrifugation supernatant, which includes the nucleus of bone cells, of bone issue homogenate with incorporation of [3H]-deoxythymidine 5'-triphosphate (dTTP). DNA synthesis activity in the femoral-diaphyseal and metaphyseal tissues of newborn rats was significantly raised with increasing age (1-21 days) after birth. The presence of dipicolinate (10(-3) M), a chelator of zinc, in the reaction mixture caused a significant decrease in DNA synthesis activity in the diaphyseal and metaphyseal tissues of newborn rats at 7 and 14 days after birth. The addition of zinc sulfate (10(-6) - 10(-4) M) resulted in a significant increase in DNA synthesis activity in the diaphyseal and metaphyseal tissues. When the diaphyseal and metaphyseal tissues of newborn rats at 7 days after birth were cultured for 24 hours in a serum-free medium containing either vehicle, zinc sulfate (10(-4) M), insulin-like growth factor-I (IGF-I; 10(-8) M) or transforming growth factor-beta (TGF-beta; 10(-10) M), bone DNA synthesis activity was significantly elevated. Culture with both zinc and IGF-I enhanced additively bone DNA synthesis activity. Such an effect was not seen in the case of zinc and TGF-beta. The effect of zinc, IGF-I, or zinc plus IGF-I in increasing bone DNA synthesis activity was completely prevented by culture with PD98059 (10(-5) M), an inhibitor of mitogen-activated protein (MAP) kinase. Also, the effect of zinc, TGF-beta. or zinc plus TGF-beta in elevating bone DNA synthesis activity was significantly inhibited by culture with staurosporine (10(-6) M), an inhibitor of protein kinase C. The present study demonstrates that zinc, like bone growth factors, has a stimulatory effect on bone DNA synthesis in newborn rats.
authors.affiliation: Laboratory of Endocrinology and Molecular Metabolism, Graduate School of Nutritional Sciences, University of Shizuoka, Japan.
authors.forename: Z J
authors.initials: ZJ
authors.lastname: Ma
authors.forename: M
authors.initials: M
authors.lastname: Yamaguchi
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001846:Bone Development / Q000187:drug effects*; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis*; D018483:Diaphyses / Q000187:drug effects / Q000254:growth & development; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005269:Femur / Q000187:drug effects / Q000254:growth & development; D005419:Flavonoids / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D010848:Picolinic Acids / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D019311:Staurosporine / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D019287:Zinc Sulfate / Q000494:pharmacology*
chemical_list: D004338:Drug Combinations; D004791:Enzyme Inhibitors; D005419:Flavonoids; D019384:Nucleic Acid Synthesis Inhibitors; D010848:Picolinic Acids; D016212:Transforming Growth Factor beta; D007334:Insulin-Like Growth Factor I; D019287:Zinc Sulfate; D004247:DNA; D020928:Mitogen-Activated Protein Kinases; D019311:Staurosporine; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; C004860:dipicolinic acid