Bone cell mitogenic action of fluoroaluminate and aluminum fluoride but not that of sodium fluoride involves upregulation of the insulin-like growth factor system

• Published in: Bone (New York, N.Y.) N.Y.), 2002-05, Vol.30 (5), p.705-711
• Main Authors: Lau, K.-H.W, Goodwin, C, Arias, M, Mohan, S, Baylink, D.J
• Format: Article
• Language: English
• Subjects: Aluminum - pharmacology; Aluminum Compounds - pharmacology; Aluminum fluoride; Biological and medical sciences; Bone cells (human); Bone Neoplasms; Cell Division - drug effects; DNA - biosynthesis; Fluorides - pharmacology; Fluorine - pharmacology; Fluoroaluminate; Fundamental and applied biological sciences. Psychology; Gene Expression - drug effects; Humans; Insulin-like growth factor; Insulin-Like Growth Factor Binding Protein 4 - genetics; Insulin-Like Growth Factor Binding Protein 5 - genetics; Insulin-Like Growth Factor II - genetics; Mitogens - pharmacology; Osteosarcoma; Proliferation; RNA, Messenger - analysis; Skeleton and joints; Sodium fluoride; Sodium Fluoride - pharmacology; Tumor Cells, Cultured - cytology; Tumor Cells, Cultured - drug effects; Tumor Cells, Cultured - physiology; Up-Regulation - drug effects; Vertebrates: osteoarticular system, musculoskeletal system
• ISSN: 8756-3282; 1873-2763
• DOI: 10.1016/S8756-3282(02)00671-3

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 μmol/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.