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Glucocorticoids Inhibit Fibronectin Synthesis and Messenger Ribonucleic Acid Levels in Cultured Fetal Rat Parietal Bones^*

GLORIA A. GRONOWICZ, MARY E. DEROME and MARY-BETH MCCARTHY

Department of Orthopedic Surgery, University of Connecticut Health Center Farmington, Connecticut 06032

Abstract

The effects of corticosterone on fibronectin production, bone growth, and morphology were examined in a mineralizing organ culture system derived from 20-day-old fetal rat parietal bones. During 4 days of culture, 1-1000 nM corticosterone had no significant effect on the increase in dry weight or on DNA content, but 100 and 1000 nM corticosterone did inhibit the increase in calcium content. Light microscopic examination of the 4-day cultures demonstrated a glucocorticoid-induced change in osteoblast shape and organization along the mineralizing front of the bone. A dose-dependent inhibition of fibronectin secretion into the medium was determined by enzyme-linked immunosorbant assay. In control cultures, fibronectin production was 0.105 ± 0.005 µg/ml-bone at 24 h and 0.397 ± 0.037 µg/ml-bone during the 72- to 96-h interval. The maximal inhibition of fibronectin secretion was 45% at 24 h and 70% at 96 h with 1000 nM corticosterone. Both immunofluorescent visualization of fibronectin staining in the tissue and a Western blot of fibronectin in the tissue showed a decrease in fibronectin levels. At 24 and 96 h, a dose- and time-dependent decrease in fibronectin mRNA transcripts was found. At 24 and 96 h, 1000 nM corticosterone produced a decrease of 42% and 62%, respectively, in fibronectin mRNA levels. Our findings show that glucocorticoids inhibit fibronectin production in developing bone. The decrease in fibronectin synthesis may contribute to altered osteoblast organization and function during bone formation. (Endocrinology 128: 1107–1114, 1991)

Footnotes

^* This work was supported by NIH Grants AR-20621 and AR-33636 (to G.A.G.).

To whom all correspondence and requests for reprints should be addressed.

Received July 25, 1990.

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