Effects of recombinant human insulin-like growth factor I and II (IGF-I/-II) and growth hormone (GH) on the growth of normal adult human osteoblast-like cells and human osteogenic sarcoma cells.
Recombinant GH and IGF-I/-II were studied for their capacity to directly influence the growth of human bone cells maintained under defined serum-free conditions. Normal human osteoblast-like cell (HOB) cultures were established from trabecular bone explants obtained from adult human femoral head samples. IGF-I and IGF-II as well as GH stimulated the growth of the HOB cultures in a dose-dependent manner. Growth stimulatory effects were also found using the human osteogenic sarcoma cell line, SaOS-2. IGF-I and -II were powerful enhancers of the SaOS-2 cell growth and their effects greatly exceeded GH effects on these cells. The role of endogenously produced IGFs was studied using a specific monoclonal antibody to IGF-I having a partial cross-reactivity with IGF-II (sm1.2B). The IGF-I stimulated HOB growth was completely neutralised by sm1.2B to the level of control+antibody which in general showed a slight stimulation compared to controls without the antibody. Interestingly, sm1.2B was not able to interfere with the action of GH on the HOB suggesting that GH effects may be attributed to an action independent of endogenous IGF-I/-II. Unlike the HOB, SaOS-2 cells were strongly inhibited by sm1.2B in control medium indicating an autocrine role of IGF-I/-II in osteosarcoma cell growth. Sm1.2B completely neutralised the stimulatory effects of IGF-I and IGF-II on the SaOS-2 cells. Moreover, GH effects on the osteogenic sarcoma cells were abolished by the anti-IGF antibody showing that GH was acting via endogenously produced IGFs.(ABSTRACT TRUNCATED AT 250 WORDS)
Scheven
B A
BA
University Hospital Utrecht, Research Group for Bone Metabolism, The Netherlands.
Hamilton
N J
NJ
Fakkeldij
T M
TM
Duursma
S A
SA
D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D013006:Growth Hormone / Q000494:pharmacology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology*; D010006:Osteoblasts / Q000166:cytology*; D012516:Osteosarcoma / Q000473:pathology*; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D013006:Growth Hormone