2,3,7,8-Tetrachlorodibenzo-p-dioxin inhibits differentiation of normal diploid rat osteoblasts in vitro.
The influence of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent halogenated aromatic hydrocarbon, on the development of bone tissue-like organization in primary cultures of normal diploid calvarial-derived rat osteoblasts was examined. Initially, when placed in culture, these cells actively proliferate while expressing genes associated with biosynthesis of the bone extracellular matrix. Then, post-proliferatively, genes are expressed that render the osteoblast competent for extracellular matrix mineralization and maintenance of structural as well as functional properties of the mature bone-cell phenotype. Our results indicate that, in the presence of TCDD, proliferation of osteoblasts was not inhibited but post-confluent formation of multicellular nodules that develop bone tissue-like organization was dramatically suppressed. Consistent with TCDD-mediated abrogation of bone nodule formation, expression of alkaline phosphatase and osteocalcin was not upregulated post-proliferatively. These findings are discussed within the context of TCDD effects on estrogens and vitamin D-responsive developmental gene expression during osteoblast differentiation and, from a broader biological perspective, on steroid hormone control of differentiation.
Gierthy
J F
JF
Wadsworth Center for Laboratories and Research, New York State Department of Health, Albany 12201-0509.
Silkworth
J B
JB
Tassinari
M
M
Stein
G S
GS
Lian
J B
JB
D000818:Animals; D015415:Biomarkers / Q000737:chemistry; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004171:Diploidy; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects*; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D051381:Rats; D012016:Reference Values
D015415:Biomarkers; D000072317:Polychlorinated Dibenzodioxins