Ionic products of bioactive glass dissolution increase proliferation of human osteoblasts and induce insulin-like growth factor II mRNA expression and protein synthesis

Bioglass 45S5 is an osteoproductive material, which resorbs by releasing it s constitutive ions into solution. Treatment with the ionic products of Bio glass 45S5 dissolution in DMEM for 4 days increased human osteoblast prolif eration to 155% of control, Two days after treatment, differential gene exp ression was analyzed by cDNA microarrays, Expression of a potent osteoblast mitogenic growth factor, insulin-like growth factor II (IGF-II), was incre ased to 290%, Additionally, there was a 168% increase in the concentration of unbound IGF-II protein in the conditioned media of treated osteoblasts. Expression levels of IGFBP-3, an IGF-II carrier protein, metalloproteinase- 2 and cathepsin-D were also increased to 200, 340, and 310% of central leve ls, respectively. Metalloproteinase-2 and cathepsin-D are proteases that cl eave IGF-II from its carrier proteins, resulting in the release of the unbo und biologically active IGF-II. We suggest that the stimulatory effect of t he ionic products of Bioglass 45S5 dissolution on osteoblast proliferation may be mediated by IGF-II. (C) 2000 Academic Press.