title: Evidence that human bone cells in culture secrete insulin-like growth factor (IGF)-II and IGF binding protein-3 but not acid-labile subunit both under basal and regulated conditions.
abstract: Insulin-like growth factors (IGFs) are found in human circulation predominantly as part of a growth hormone (GH)-dependent complex of 125-150 kD, which is composed of three subunits: IGF-I or IGF-II, an acid stable IGF binding protein (IGFBP)-3, and an acid labile subunit (ALS). Although recent studies demonstrate that a number of cell types in culture secrete IGFs and IGFBP-3, very little is known with regard to the origin of circulating ALS. To test the hypothesis that human bone cells (HBCs), which produce abundant amounts of IGF-II and IGFBP-3, also produce ALS, we measured the IGF-I, IGF-II, IGFBP-3, and ALS levels using specific radioimmunoassays (RIAs) in the conditioned medium (CM) of untransformed normal HBCs and SaOS-2 osteosarcoma cells treated with various effectors (IGF-II, osteogenic protein-1 [OP-1, bone morphogenetic protein-7] and human GH) for 48 h. No detectable levels (< 3 ng/ml) of ALS were found in the CM of various HBC types under basal conditions. In contrast, CM collected from liver explants in culture contained significant amount of ALS prepared and assayed under identical conditions. The IGF-I level was also undetectable in the CM of various HBC types. In the IGF-II (3, 30 ng/ml)-treated HBC CM, the IGFBP-3 level was increased in a dose-dependent manner but neither IGF-I nor ALS could be detected. In the SaOS-2 cell culture, OP-1 (1, 100 ng/ml) increased both IGF-II and IGFBP-3 secretion but neither ALS nor IGF-I secretion. Treatment of HBCs with GH (1, 10, 100 ng/ml) had no significant effect on the secretion of either IGF-I, IGF-II, IGFBP-3, or ALS.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Medicine, Loma Linda University, California, USA.
authors.forename: S
authors.initials: S
authors.lastname: Kanzaki
authors.forename: R C
authors.initials: RC
authors.lastname: Baxter
authors.forename: R
authors.initials: R
authors.lastname: Knutsen
authors.forename: D J
authors.initials: DJ
authors.lastname: Baylink
authors.forename: S
authors.initials: S
authors.lastname: Mohan
mesh_terms: D000328:Adult; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D001859:Bone Neoplasms / Q000473:pathology; D001842:Bone and Bones / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D016895:Culture Media, Serum-Free; D006023:Glycoproteins / Q000378:metabolism*; D013006:Growth Hormone / Q000494:pharmacology; D006131:Growth Inhibitors / Q000378:metabolism*; D006801:Humans; D007223:Infant; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism* / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008970:Molecular Weight; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D012516:Osteosarcoma / Q000473:pathology; D011506:Proteins / Q000494:pharmacology; D011863:Radioimmunoassay; D011994:Recombinant Proteins / Q000494:pharmacology; D012272:Ribs / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D012886:Skull / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013002:Somatomedins / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D017077:Culture Media, Conditioned; D016895:Culture Media, Serum-Free; D006023:Glycoproteins; D006131:Growth Inhibitors; D018972:Insulin-Like Growth Factor Binding Protein 3; D011506:Proteins; D011994:Recombinant Proteins; D013002:Somatomedins; D016212:Transforming Growth Factor beta; C075944:insulin-like growth factor binding protein, acid labile subunit; D007335:Insulin-Like Growth Factor II; D013006:Growth Hormone