7512304

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1

Insulin-like growth factor binding protein 4 (IGFBP-4) is secreted by normal human osteoblast-like cells (hOB) and is a potent inhibitor of insulin-like growth factor (IGF) action in vitro. In previous studies, IGF treatment of hOB in culture led to markedly reduced medium levels of IGFBP-4 as detected by western ligand blotting. In the present study, incubation of hOB-conditioned medium (hOB-CM) with IGF under cell-free conditions resulted in a similar loss of IGFBP-4. Both IGF-I and IGF-II were capable of inducing a decrease in IGFBP-4; however, IGF-II was more effective. When the six characterized IGFBP were added to hOB-CM, only IGFBP-4 disappeared in response to IGF-II addition. This IGF-regulated loss of IGFBP-4 was inhibited by metalloproteinase inhibitors and appeared to be due to a proteinase that cleaved IGFBP-4 in 18 and 14 kD fragments identified by western immunoblotting. Conditioned media from eight of eight different donor hOB lines tested exhibited IGFBP-4 proteinase activity. To assess the biologic consequences of IGF-II-induced IGFBP-4 proteolysis, we treated hOB with IGF-II for 5 h, which decreased medium IGF-BP-4 by 70%, and then measured IGF-I and insulin stimulation of [3H]thymidine incorporation. IGF-II itself was not mitogenic and had no effect on insulin-stimulated [3H]thymidine incorporation. However, pretreatment of cultured hOB with IGF-II enhanced IGF-I-stimulated [3H]thymidine incorporation threefold.(ABSTRACT TRUNCATED AT 250 WORDS)

eng

IM

MEDLINE

0884-0431

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111-7

pubmed-meshheading:7512304-Adult, pubmed-meshheading:7512304-Blotting, Western, pubmed-meshheading:7512304-Carrier Proteins, pubmed-meshheading:7512304-Cells, Cultured, pubmed-meshheading:7512304-Culture Media, Conditioned, pubmed-meshheading:7512304-Electrophoresis, Polyacrylamide Gel, pubmed-meshheading:7512304-Female, pubmed-meshheading:7512304-Growth Hormone, pubmed-meshheading:7512304-Humans, pubmed-meshheading:7512304-Insulin, pubmed-meshheading:7512304-Insulin-Like Growth Factor Binding Protein 4, pubmed-meshheading:7512304-Insulin-Like Growth Factor I, pubmed-meshheading:7512304-Insulin-Like Growth Factor II, pubmed-meshheading:7512304-Ligands, pubmed-meshheading:7512304-Male, pubmed-meshheading:7512304-Metalloendopeptidases, pubmed-meshheading:7512304-Osteoblasts, pubmed-meshheading:7512304-Pregnancy-Associated Plasma Protein-A, pubmed-meshheading:7512304-Recombinant Proteins, pubmed-meshheading:7512304-Somatomedins

Regulation of insulin-like growth factor binding protein 4 by a specific insulin-like growth factor binding protein 4 proteinase in normal human osteoblast-like cells: implications in bone cell physiology.

Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't