REGULATION OF INSULIN-LIKE GROWTH-FACTOR BINDING PROTEIN-5 MESSENGER-RIBONUCLEIC-ACID EXPRESSION AND PROTEIN AVAILABILITY IN RAT OSTEOBLAST-LIKE CELLS

被引:64
|
作者
CONOVER, CA [1 ]
BALE, LK [1 ]
CLARKSON, JT [1 ]
TORRING, O [1 ]
机构
[1] KAROLINSKA HOSP,DEPT ENDOCRINOL,S-10401 STOCKHOLM 60,SWEDEN
关键词
D O I
10.1210/en.132.6.2525
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 M(r) 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 (Sm1.2) 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.
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页码:2525 / 2530
页数:6
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