Expression, effects, and fate of IGFBP-5 are different in normal and malignant osteoblastic cells.
Normal osteoblasts from newborn rat calvaria and human osteosarcoma (Saos-2) cells express IGFBP-5 mRNA. IGF I increases IGFBP-5 mRNA levels in both cell types, whereas retinoic acid stimulates IGFBP-5 mRNA expression in calvaria but suppresses it in Saos-2 cells. IGFBP-5 mRNA expression is stimulated in normal bone cells by parathyroid hormone. 30 nM IGFBP-5 stimulates 3H-thymidine incorporation in calvaria (which produce IGF I contributing to basal proliferation in serum-free medium) but not in Saos-2 cells which produce little IGF I and IGF II. Among the 5 rhIGFBPs tested (IGFBP-2 to -6), only IGFBP-5 stimulates DNA synthesis in calvaria cells, and only IGFBP-6 in Saos-2 cells. RhIGFBP-5 displays a short half-life (approximately 30 min) in serum-free medium of calvaria cells and a long half-life (approximately 15 h) in the medium of Saos-2 cells. Fragments of 20 and 14 kDa accumulate in the media of both cell types. Intact (31 kDa) IGFBP-5 is associated and remains with the extracellular matrix of mature calvaria osteoblasts but not of Saos-2 cells. Among the IGFBPs produced IGFBP-5 is unique with regard to its marked affinity to matrix of normal bone cells, its short half-life when released, and its stimulatory effects on DNA synthesis.
Schmid
C
C
Department of Medicine, University Hospital, Zürich, Switzerland.
Schläpfer
I
I
Gosteli-Peter
M A
MA
Froesch
E R
ER
Zapf
J
J
D000818:Animals; D018507:Gene Expression Regulation, Developmental; D006207:Half-Life; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000235:genetics*; D018976:Insulin-Like Growth Factor Binding Protein 6 / Q000378:metabolism; D008970:Molecular Weight; D010006:Osteoblasts / Q000378:metabolism*; D012516:Osteosarcoma / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014404:Tubulin / Q000235:genetics; D014407:Tumor Cells, Cultured
D018972:Insulin-Like Growth Factor Binding Protein 3; D018975:Insulin-Like Growth Factor Binding Protein 5; D018976:Insulin-Like Growth Factor Binding Protein 6; D012333:RNA, Messenger; D014404:Tubulin