Sodium fluoride as an initiator of osteogenesis from embryonic mesenchyme in vitro

Abstract

Sodium fluoride, which preferentially and rapidly becomes incorporated into bone, is a potent stimulator of bone formation. As such, it has been used to increase total bone mass in patients suffering from osteoporosis. How NaF stimulates bone formation is little understood. Farley et al. ( Science 222:330–332, 1983) demonstrated that NaF has a direct effect on proliferation and bone-forming activity of isolated bone cells and of bones exposed to NaF in vitro, that is, NaF stimulates ongoing osteogenesis. In this study, we ask whether NaF can allow preosteogenic embryonic mesenchymal cells to undergo their initial differentiation into osteoblasts and to deposit bone matrix. The mesenchymal cells were from mandibular mesenchyme from embryonic chicks. Mesenchyme from the mandibular arches has to undergo a tissue interaction with mandibular arch epithelium until 4 1 2 days of incubation before osteogenesis can be initiated. Therefore, mandibular arch mesenchyme from younger embryos ( 3 1 2 -4 days), enzymatically freed from its epithelium, was used to provide a source of uninduced preosteogenic cells. Mesenchyme was cultured in the presence or absence of NaF (10 −5M) in both serum-free and serum-supplemented medium. Osteogenesis was only initiated when NaF was present and only in the presence of serum. Mesenchyme from older embryos that failed to undergo osteogenesis in serum-free medium did form bone in the presence of NaF. It is concluded that preosteogenic embryonic mesenchyme can be stimulated by NaF to differentiate into osteoblasts and to deposit bone matrix. Therefore, not only is NaF a potent stimulator of ongoing osteogenesis from already differentiated osteoblasts, but also it can substitute for a normal bone inducer and permit initiation of osteogenesis from embryonic mesenchyme.