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Am J Physiol Endocrinol Metab 279: E570-E576, 2000;
0193-1849/00 $5.00
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Vol. 279, Issue 3, E570-E576, September 2000

Transcriptional regulation of connective tissue growth factor by cortisol in osteoblasts

Renata C. Pereira1, Deena Durant1, and Ernesto Canalis1,2,3

Departments of 1 Research and 2 Medicine, Saint Francis Hospital and Medical Center, Hartford, 06105; and 3 School of Medicine, University of Connecticut, Farmington, Connecticut 06030

Glucocorticoids have important effects on osteoblastic function. Connective tissue growth factor (CTGF)/insulin-like growth factor binding protein-related protein 2 (IGFBP-rP2) plays a role in cell adhesion and function. We examined the regulation of CTGF/IGFBP-rP2 synthesis in cultures of osteoblast-enriched cells from 22-day fetal rat calvariae (Ob cells). Cortisol caused a time- and dose-dependent increase in CTGF/IGFBP-rP2 mRNA levels in Ob cells. Cycloheximide did not preclude the effect, indicating that it was not protein synthesis dependent. Cortisol increased the rate of CTGF/IGFBP-rP2 transcription and, in transcriptionally arrested Ob cells, did not modify the decay of the transcript. Parathyroid hormone decreased, whereas transforming growth factor-beta and, to a lesser extent, bone morphogenetic protein 2 increased CTGF/IGFBP-rP2 mRNA levels, but other hormones and growth factors had no effect. In conclusion, cortisol stimulates CTGF/IGFBP-rP2 transcription in Ob cells. Because CTGF/IGFBP-rP2 binds IGFs, its increased expression could be relevant to the actions of cortisol in bone.

skeletal cells; insulin-like growth factor; insulin-like growth factor binding proteins; glucocorticoids; bone formation


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