Glucocorticoid regulation of insulin-like growth factor-binding protein expression in normal human osteoblast-like cells

Ryo Okazaki, B. Lawrence Riggs, Cheryl A Conover

Research output: Contribution to journalArticle

134 Citations (Scopus)

Abstract

Glucocorticoid (GC) modulates insulin-like growth factor (IGF) action in bone through mechanisms that are complex and not well understood. Because the family of IGF-binding proteins (IGFBP-1 through -6) is important in the regulation of IGF availability and bioactivity, we examined the effect of GC on IGFBP expression in normal human osteoblast-like (hOB) cells. As assessed by Western ligand blot, hOB cells release IGFBP-3, IGFBP-4, and a 31- kilodalton IGFBP, which appeared to be IGFBP-5. Northern analysis revealed that hOB cells express abundant IGFBP-3, IGFBP-4, IGFBP-5, and IGFBP-6 mRNA, with barely detectable IGFBP-1 mRNA. GC treatment resulted in time- and dose- dependent decreases in IGFBP-3, IGFBP-4, and 31-kilodalton IGFBP levels in culture medium, with corresponding decreases in IGFBP-3, IGFBP-4, and IGFBP- 5 mRNA levels. In addition, GC treatment increased steady state levels of IGFBP-1 mRNA and did not alter IGFBP-6 mRNA levels. Although hOB cells secrete an acid-activated IGFBP-3 protease and an IGF-dependent IGFBP-4 protease, GC had little effect on these protease activities and did not alter degradation of the secreted IGFBPs. Our results indicate that GC has dramatic effects on IGFBP gene expression and suggest that differential regulation of IGFBPs by GC may modulate hOB cell responsiveness to IGFs.

Original languageEnglish (US)
Pages (from-to)126-132
Number of pages7
JournalEndocrinology
Volume134
Issue number1
DOIs
StatePublished - Jan 1994

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Insulin-Like Growth Factor Binding Proteins
Osteoblasts
Glucocorticoids
Insulin-Like Growth Factor Binding Protein 4
Insulin-Like Growth Factor Binding Protein 1
Insulin-Like Growth Factor Binding Protein 3
Insulin-Like Growth Factor Binding Protein 5
Somatomedins
Insulin-Like Growth Factor Binding Protein 6
Messenger RNA
Pregnancy-Associated Plasma Protein-A
Culture Media
Peptide Hydrolases
Western Blotting
Ligands
Gene Expression
Bone and Bones
Acids

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Glucocorticoid regulation of insulin-like growth factor-binding protein expression in normal human osteoblast-like cells. / Okazaki, Ryo; Riggs, B. Lawrence; Conover, Cheryl A.

In: Endocrinology, Vol. 134, No. 1, 01.1994, p. 126-132.

Research output: Contribution to journalArticle

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