Insulin-like growth factor-binding protein-1 expression in cultured human bone cells: Regulation by insulin and glucocorticoid

Cheryl A. Conover, Phillip Lee, B. Lawrence Riggs, David R. Powell

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Insulin-like growth factors (IGFs) and their specific regulatory binding proteins (JGFBPs) are postulated to play a key role in bone metabolism. To date, IGFBP-2 through -6 have been characterized in bone cell systems. In this study we focused on IGFBP-1. Primary cultures of normal human osteoblasts derived from trabecular bone (hOB cells) expressed low levels of IGFBP-1 messenger RNA (mRNA), as determined by Northern analyses. Treatment of hOB cells with 1 μM cortisol or 100 nM dexamethasone for 20 h stimulated IGFBP-1 mRNA expression 5-fold and increased levels of immunoassayable IGFBP- 1 in the conditioned medium 3-fold. Estradiol and progesterone had no effect. IGFBP-1 expression was not observed in U-2, TE-85, or MG-63 human osteosarcoma cell lines or in normal human fibroblasts. Insulin (1-100 nM) potently inhibited both basal and glucocorticoid-stimulated IGFBP-1 expression in hOB cells. Insulin had little or no effect on steady state levels of the other IGFBP mRNA. A monoclonal antibody to the insulin receptor blocked insulin binding to insulin receptors and completely prevented insulin-induced suppression of IGFBP-1. In summary, we have documented IGFBP- 1 mRNA and protein expression in normal nontransformed human osteoblastic cells. This expression was stimulated by glucocorticoids and inhibited by insulin in a manner similar to IGFBP-1 regulation in hepatocytes. Insulin acts through insulin receptors on hOB cells. We postulate that IGFBP-1 produced by osteoblasts in vivo can modulate local actions of IGF on bone formation in response to changes in glucocorticoid and insulin concentrations.

Original languageEnglish
Pages (from-to)3295-3301
Number of pages7
JournalEndocrinology
Volume137
Issue number8
DOIs
StatePublished - 1996
Externally publishedYes

Fingerprint

Insulin-Like Growth Factor Binding Protein 1
Glucocorticoids
Insulin
Bone and Bones
Insulin Receptor
Messenger RNA
Somatomedins
Osteoblasts
Insulin-Like Growth Factor Binding Protein 2
Insulin-Like Growth Factor Binding Proteins
Osteosarcoma
Conditioned Culture Medium
Osteogenesis
Dexamethasone
Progesterone
Hydrocortisone
Hepatocytes
Estradiol
Carrier Proteins
Fibroblasts

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Insulin-like growth factor-binding protein-1 expression in cultured human bone cells : Regulation by insulin and glucocorticoid. / Conover, Cheryl A.; Lee, Phillip; Riggs, B. Lawrence; Powell, David R.

In: Endocrinology, Vol. 137, No. 8, 1996, p. 3295-3301.

Research output: Contribution to journalArticle

Conover, Cheryl A. ; Lee, Phillip ; Riggs, B. Lawrence ; Powell, David R. / Insulin-like growth factor-binding protein-1 expression in cultured human bone cells : Regulation by insulin and glucocorticoid. In: Endocrinology. 1996 ; Vol. 137, No. 8. pp. 3295-3301.
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