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Characterization of human fetal osteoblasts by microarray analysis following stimulation with 58S bioactive gel-glass ionic dissolution products.

Christodoulou I, Buttery LD, Tai G, Hench LL, Polak JM

Tissue Engineering and Regenerative Medicine (TERM) Centre, Imperial College Faculty of Medicine, Chelsea and Westminster Campus, 369 Fulham Road, London SW10 9NH, UK.

Bioactive glasses dissolve upon immersion in culture medium, releasing their constitutive ions in solution. There is evidence suggesting that these ionic dissolution products influence osteoblast-specific processes. Here, we investigated the effect of 58S sol-gel-derived bioactive glass (60 mol % SiO2, 36 mol % CaO, 4 mol % P2O5) dissolution products on primary osteoblasts derived from human fetal long bone explant cultures (hFOBs). We used U133A human genome GeneChip oligonucleotide arrays to examine 22,283 transcripts and variants, which represent over 18,000 well-substantiated human genes. Hybridization of samples (biotinylated cRNA) derived from monolayer cultures of hFOBs on the arrays revealed that 10,571 transcripts were expressed by these cells, with high confidence. These included transcripts representing osteoblast-related genes coding for growth factors and their associated molecules or receptors, protein components of the extracellular matrix (ECM), enzymes involved in degradation of the ECM, transcription factors, and other important osteoblast-associated markers. A 24-h treatment with a single dosage of ionic products of sol-gel 58S dissolution induced the differential expression of a number of genes, including IL-6 signal transducer/gp130, ISGF-3/STAT1, HIF-1 responsive RTP801, ERK1 p44 MAPK (MAPK3), MAPKAPK2, IGF-I and IGFBP-5. The over 2-fold up-regulation of gp130 and MAPK3 and down-regulation of IGF-I were confirmed by real-time RT-PCR analysis. These data suggest that 58S ionic dissolution products possibly mediate the bioactive effect of 58S through components of the IGF system and MAPK signaling pathways.

Published 13 April 2006 in J Biomed Mater Res B Appl Biomater, 77(2): 431-46.
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