2,3,7,8‐Tetrachlorodibenzo‐p‐dioxin inhibits differentiation of normal diploid rat osteoblasts in vitro

Abstract

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.