Multiple levels of steroid hormone-dependent control of osteocalcin during osteoblast differentiation: Glucocorticoid regulation of basal and vitamin D stimulated gene expression

Victoria Shalhoub, Fauzia Aslam, Ellen Breen, André Van Wijnen, Rita Bortell, Gary S. Stein, Janet L. Stein, Jane B. Lian

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

We have examined the contribution of transcriptional mechanisms to the pleiotropic effects of glucocorticoids on basal and vitamin D stimulated expression of the developmentally regulated bone-specific osteocalcin (OC) gene. OC expression was systematically investigated at the level of protein, mRNA, and newly synthesized transcripts during maturation of the bone cell phenotype in cultures of fetal rat calvarial-derived osteoblasts. Our results indicate that transcriptional control of basal and hormone-regulated OC expression predominates in immature osteoblasts prior to matrix mineralization. However, in mature osteoblasts OC expression is controlled primarily by posttranscriptional mechanisms reflected by elevated mRNA levels with a decline in transcription. Vitamin D, alone or in combination with Dex, is a significant factor contributing to mRNA stabilization in mature osteoblasts with a mineralized extracellular matrix. Transcriptional modifications in response to Dex are reflected by quantitative differences between proliferating and mature osteoblasts in the formation of glucocorticoid receptor binding complexes at the proximal OC glucocorticoid response element. Vitamin D and glucocorticoid receptor mRNA levels are significantly higher in mature osteoblasts than in early stage bone cells. However, receptor complexes do not appear to be rate limiting in proliferating osteoblasts when the OC gene is not transcribed. Our results indicate (1) developmental stage-specific effects of steroid hormone on transcriptional regulation of bone expressed genes, and (2) inverse relationships between levels of transcription and cellular representation of mRNA with OC message stabilized in mature osteoblasts.

Original languageEnglish (US)
Pages (from-to)154-168
Number of pages15
JournalJournal of cellular biochemistry
Volume69
Issue number2
DOIs
StatePublished - May 1 1998

Keywords

  • Dexamethasone
  • Gene regulation
  • Glucocorticoid receptor
  • MRNA stability
  • Osteopontin
  • Rat calvarial osteoblasts
  • Transcription
  • Vitamin D receptor

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Multiple levels of steroid hormone-dependent control of osteocalcin during osteoblast differentiation: Glucocorticoid regulation of basal and vitamin D stimulated gene expression'. Together they form a unique fingerprint.

  • Cite this