Transcriptional regulation of connective tissue growth factor by cortisol in osteoblasts

Abstract

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-β 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.