Bone cell mitogenic action of fluoroaluminate and aluminum fluoride but not that of sodium fluoride involves upregulation of the insulin-like growth factor system.
The fluoroaluminate (AlF(4)(-)) ion and sodium fluoride (NaF) have previously been shown to be bone cell mitogens. This study sought to determine whether the bone cell mitogenic action of AlF(4)(-) and/or NaF would involve the insulin-like growth factor (IGF) regulatory system. We evaluated the effect of mitogenic doses of AlF(4)(-) and NaF on the mRNA levels and the protein level (in conditioned media [CM]) of several components of the IGF system (i.e., IGF-2, IGF binding protein [IGFBP]-4, and IGFBP-5) in human TE85 osteosarcoma cells. Aluminum fluoride (AlF(3)) was included for comparison. NaF, AlF(3), and AlF(4)(-), each at 50-100 micromol/L, increased [3H]thymidine incorporation in TE85 cells. Mitogenic concentrations of AlF(3) and AlF(4)(-): (1) increased the mRNA (up to twofold after 24 h treatment) and protein (in CM) levels (up to 2.5-fold after 48 h treatment) of IGF-2; (2) increased the mRNA level (twofold) and the protein level in CM (up to threefold) of stimulatory IGFBP-5; and (3) either reduced slightly or had no effect on the mRNA and protein (in CM) levels of the inhibitory IGFBP-4. Conversely, mitogenic concentrations of NaF had no significant effects on the protein (in CM) or mRNA level of IGF-2, IGFBP-4, or IGFBP-5. The addition of an inhibitory concentration of IGFBP-4 completely abolished the bone cell mitogenic activity of AlF(3) and AlF(4)(-) but not that of NaF. The findings of this study provide strong evidence that the bone cell mitogenic activity of AlF(4)(-) and AlF(3), but not that of NaF, is mediated by the upregulation of the IGF regulatory system.
Lau
K-H  William
KH
Musculoskeletal Disease Center (151), Jerry L. Pettis Memorial VA Medical Center, 11201 Benton Street, Loma Linda, CA 92357, USA. laub@lom.med.va.gov
Goodwin
C
C
Arias
M
M
Mohan
S
S
Baylink
D J
DJ
D000535:Aluminum / Q000494:pharmacology*; D017607:Aluminum Compounds / Q000494:pharmacology*; D001859:Bone Neoplasms; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D005459:Fluorides / Q000494:pharmacology*; D005461:Fluorine / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000235:genetics; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000235:genetics; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D008934:Mitogens / Q000494:pharmacology; D012516:Osteosarcoma; D012333:RNA, Messenger / Q000032:analysis; D012969:Sodium Fluoride / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects
D017607:Aluminum Compounds; D018974:Insulin-Like Growth Factor Binding Protein 4; D018975:Insulin-Like Growth Factor Binding Protein 5; D008934:Mitogens; D012333:RNA, Messenger; C053629:fluoroaluminum; D005461:Fluorine; D007335:Insulin-Like Growth Factor II; D012969:Sodium Fluoride; D004247:DNA; D000535:Aluminum; D005459:Fluorides; C032311:aluminum fluoride