Regulation of insulin-like growth factor binding protein-5 messenger ribonucleic acid expression and protein availability in rat osteoblast-like cells

Cheryl A. Conover, Laurie K. Bale, Jay T. Clarkson, Ove T∅Rring

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Abstract

PTH treatment of UMR 106-01 rat osteosarcoma cells increased 20-to 100-fold medium levels of a discrete insulin-like growth factor binding protein (IGFBP) with Mr of 29K. Northern analysis of UMR cellular RNA hybridized with a specific IGFBP-5 complementary DNA probe indicated a 6.0-kilobase transcript induced within 2 h in PTH-treated cells. IGFBP-5 messenger RNA (mRNA) abundance was maximal around 6 h and remained elevated after 24 h of treatment. Another rat osteosarcoma cell line (ROS 17/2.8) did not express IGFBP-5 mRNA and did not secrete 29K IGFBP. Induction of IGFBP-5 mRNA by PTH was blocked when RNA synthesis in UMR cells was inhibited by actinomycin D. (Bu)2cAMP mimicked the effect of PTH on IGFBP- 5 mRNA expression and protein secretion. In addition, a monoclonal antibody against IGF-I (Sml.2) inhibited the PTH-induced increase in medium IGFBP-5 without influencing IGFBP-5 transcript levels. Direct addition of IGF-I to UMR cell cultures increased medium IGFBP-5 levels approximately 14-fold, with a modest effect on IGFBP-5 mRNA levels. Studies comparing IGF-I, IGF-II, different IGF-I analogs, and insulin indicated that the predominant IGF effect on IGFBP-5 accumulation was type I IGF receptor independent. Thus, in UMR 106-01 cells, PTH and IGF-I increase extracellular concentrations of IGFBP-5 via distinct but coordinate mechanisms; PTH acts primarily to induce IGFBP-5 mRNA expression through a cAMP- mediated mechanism, and IGF-I appears to interact directly with IGFBP-5 protein to promote its accumulation.

Original languageEnglish (US)
Pages (from-to)2525-2530
Number of pages6
JournalEndocrinology
Volume132
Issue number6
DOIs
StatePublished - Jun 1993

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ASJC Scopus subject areas

  • Endocrinology

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