Fluoride-stimulated [3H]thymidine uptake in a human osteoblastic osteosarcoma cell line is dependent on transforming growth factor beta.
Controversy exists regarding the effect of fluoride on human osteoblast proliferation. To learn more of the cellular action of fluoride, we chose the clonal osteoblast cell line HOS TE85 as a model system. In these phenotypically osteoblast-like cells, sodium fluoride stimulated [3H]thymidine incorporation in a dose-dependent manner over the concentration range 1 x 10(-5)-2 x 10(-4) M. The fluoride-induced stimulation of [3H]thymidine uptake was dependent on cell density, being optimal at subconfluent cell numbers. Stimulation of [3H]thymidine uptake was inhibited by anti-transforming growth factor beta but not by antibody to insulin-like growth factor I or beta 2-microglobulin. Transforming growth factor beta was shown to be a biphasic stimulator of [3H]thymidine uptake in HOS TE85, with maximal stimulation occurring at 0.5 nM transforming growth factor beta. In the presence of fluoride the cells were more sensitive to stimulation by this growth factor, with maximum effect occurring at 0.1 nM. Fluoride did not increase mRNA for transforming growth factor beta following either 8 or 24 h of exposure. We conclude that fluoride activates osteoblast proliferation by modulating the cellular sensitivity to transforming growth factor beta, a known stimulator of bone growth.
Reed
B Y
BY
Department of Radiology, Southwestern Medical Center, Dallas, Texas.
Zerwekh
J E
JE
Antich
P P
PP
Pak
C Y
CY
D000906:Antibodies; D015152:Blotting, Northern; D002452:Cell Count / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D012516:Osteosarcoma; D012333:RNA, Messenger / Q000032:analysis; D012969:Sodium Fluoride / Q000494:pharmacology*; D013056:Spectrophotometry, Ultraviolet; D013936:Thymidine / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology; D014407:Tumor Cells, Cultured
D000906:Antibodies; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D012969:Sodium Fluoride; D004247:DNA; D013936:Thymidine