Secretion of insulinlike growth factor I and insulinlike growth factor-binding proteins by murine bone marrow stromal cells

S. L. Abboud, C. R. Bethel, D. C. Aron

Research output: Contribution to journalArticlepeer-review

79 Scopus citations

Abstract

Insulin-like growth factor I (IGF-I) stimulates hematopoiesis. We examined whether bone marrow stromal cells synthesize IGF-I. Secretion of IGF-I immunoreactivity by cells from TC-1 murine bone marrow stromal cells was time-dependent and inhibited by cycloheximide. Gel filtration chromatography under denaturing conditions of TC-1 conditioned medium demonstrated two major peaks of apparent IGF-I immunoreactivity with molecular weights of ~ 7.5-8.0 kD, the size of native IGF-I, and > 25 kD. Expression of IGF-I mRNA was identified by both RNase protection assay and reverse transcription/polymerase chain reaction. To determine whether the > 25-kD species identified by RIA possessed IGF-binding activity, a potential cause of artifactual IGF-I immunoreactivity, charcoal adsorption assay of these gel filtration fractions was performed. The peak of IGF-binding activity coeluted with apparent IGF-I immunoreactivity suggesting that TC-1 cells secrete IGF-binding protein(s). Unfractionated conditioned medium exhibited linear dose-dependent increase in specific binding of [125I]-IGF-I with a pattern of displacement (IGF-I and IGF-II >>> insulin) characteristic of IGF-binding proteins. Western ligand analysis of conditioned medium showed three IGF-I binding species of ~ 31, 38, and 40 kD. These data indicate that TC-1 bone marrow stromal cells synthesize and secrete IGF-I and IGF-binding proteins and constitute a useful model system to study their regulation and role in hematopoiesis.

Original languageEnglish (US)
Pages (from-to)470-475
Number of pages6
JournalJournal of Clinical Investigation
Volume88
Issue number2
DOIs
StatePublished - 1991

Keywords

  • Bone marrow stroma
  • Growth factor
  • Growth factor binding proteins

ASJC Scopus subject areas

  • Medicine(all)

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