title: Dose- and time-dependent effect of bioactive gel-glass ionic-dissolution products on human fetal osteoblast-specific gene expression.
abstract: Bioactive glasses dissolve upon immersion in culture medium, and release their constitutive ions into solution. There has been some evidence suggesting that these ionic-dissolution products influence osteoblast-specific processes. Here, the effect of 58S sol-gel-derived bioactive glass (60% SiO(2), 36% CaO, 4% P(2)O(5), in molar percentage) on primary osteoblasts derived from human fetal long bone explant cultures is investigated, and it is hypothesized that critical concentrations of sol-gel-dissolution products (consisting of a combination of simple inorganic ions) can enhance osteoblast phenotype in vitro by affecting the expression of a number of genes associated with the differentiation and extracellular matrix deposition processes. Cells were exposed to a range of 58S dosages continuously for a period of 4-14 days in monolayer cultures. Quantitative real-time RT-PCR analysis of a panel of osteoblast-specific markers showed a varied gene expression pattern in response to the material. The highest concentration of Ca and Si tested (96 and 50 ppm, respectively) promoted upregulation of gene expression for most markers (including alkaline phosphatase, osteocalcin, and osteopontin) at the latest time point, compared to non-58S-treated control, although this observation was not statistically significant. The same 58S concentration produced higher ALP activity levels and increased proliferation throughout the culture period, compared to lower dosages tested; however, the results generated were again not statistically significant. The data overall suggest that no significant effect can be ascribed to the ionic products of 58S bioactive gel-glass dissolution tested here and their ability to stimulate osteoblastic marker gene expression.
authors.affiliation: Tissue Engineering and Regenerative Medicine (TERM) Centre, Imperial College, Faculty of Medicine, Chelsea & Westminster Campus, London, UK.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Christodoulou
authors.forename: Lee D K
authors.initials: LD
authors.lastname: Buttery
authors.forename: Priya
authors.initials: P
authors.lastname: Saravanapavan
authors.forename: Guangping
authors.initials: G
authors.lastname: Tai
authors.forename: Larry L
authors.initials: LL
authors.lastname: Hench
authors.forename: Julia M
authors.initials: JM
authors.lastname: Polak
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D001672:Biocompatible Materials; D001842:Bone and Bones / Q000196:embryology*; D002118:Calcium / Q000737:chemistry; D049109:Cell Proliferation; D002478:Cells, Cultured; D003094:Collagen / Q000737:chemistry; D017077:Culture Media, Conditioned / Q000494:pharmacology; D017931:DNA Primers / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D005091:Exons; D005782:Gels; D005786:Gene Expression Regulation; D018507:Gene Expression Regulation, Developmental; D005898:Glass / Q000737:chemistry*; D006801:Humans; D007477:Ions; D010006:Osteoblasts / Q000378:metabolism*; D015675:Osteocalcin / Q000378:metabolism; D053495:Osteopontin; D010641:Phenotype; D012313:RNA / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012795:Sialoglycoproteins / Q000378:metabolism; D012825:Silicon / Q000737:chemistry; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D001672:Biocompatible Materials; D017077:Culture Media, Conditioned; D017931:DNA Primers; D005782:Gels; D007477:Ions; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; C448994:bioactive glass 58S; D015675:Osteocalcin; D053495:Osteopontin; D012313:RNA; D003094:Collagen; D000469:Alkaline Phosphatase; D002118:Calcium; D012825:Silicon