Transcriptional regulation of connective tissue growth factor by cortisol in osteoblasts

Glucocorticoids have important effects on osteoblastic function. Connective tissue growth factor (CTGF)/insulin-like growth factor binding protein-rel ated protein 2 (IGFBP-rP2) plays a role in cell adhesion and function. We e xamined the regulation of CTGF/IGFBP-rP2 synthesis in cultures of osteoblas t-enriched cells from 22-day fetal rat calvariae (Ob cells). Cortisol cause d a time- and dose-dependent increase in CTGF/IGFBP-rP2 mRNA levels in Ob c ells. 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 transfo rming growth factor-beta and, to a lesser extent, bone morphogenetic protei n 2 increased CTGF/IGFBP-rP2 mRNA levels, but other hormones and growth fac tors had no effect. In conclusion, cortisol stimulates CTGF/IGFBP-rP2 trans cription in Ob cells. Because CTGF/IGFBP-rP2 binds IGFs, its increased expr ession could be relevant to the actions of cortisol in bone.