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- Title
Stimulatory effect of zinc on deoxyribonucleic acid synthesis in bone growth of newborn rats: enhancement with zinc and insulin-like growth factor-I.
- Authors
Ma, Z.J.; Yamaguchi, M.
- 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.
- Subjects
ZINC; DNA; BONE growth; CENTRIFUGATION; BONE cells; PROTEIN kinases; AGE distribution; ALKALOIDS; ANIMAL experimentation; ANIMAL populations; CELL culture; COMBINATION drug therapy; DOSE-effect relationship in pharmacology; ENZYME inhibitors; FEMUR; FLAVONOIDS; GROWTH factors; PYRIDINE; RATS; SOMATOMEDIN; TRANSFERASES; ZINC sulfate; BONE shafts; PHARMACODYNAMICS
- Publication
Calcified Tissue International, 2001, Vol 69, Issue 3, p158
- ISSN
0171-967X
- Publication type
journal article
- DOI
10.1007/s00223-001-2010-1