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-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.
Pereira
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RC
Department of Research, Saint Francis Hospital and Medical Center, Hartford, CT 06105, USA.
Durant
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Canalis
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D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology; D002467:Cell Nucleus / Q000235:genetics; D002478:Cells, Cultured; D055513:Connective Tissue Growth Factor; D003513:Cycloheximide / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D006133:Growth Substances / Q000096:biosynthesis* / Q000235:genetics; D006854:Hydrocortisone / Q000494:pharmacology*; D017874:Immediate-Early Proteins / Q000096:biosynthesis* / Q000235:genetics; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D014158:Transcription, Genetic / Q000187:drug effects*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; C526316:CCN2 protein, rat; D006133:Growth Substances; D017874:Immediate-Early Proteins; D018971:Insulin-Like Growth Factor Binding Protein 2; D036341:Intercellular Signaling Peptides and Proteins; D010281:Parathyroid Hormone; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D055513:Connective Tissue Growth Factor; D003513:Cycloheximide; D006854:Hydrocortisone