Christodoulou Ioannis, Buttery Lee D K, Tai Guangping, Hench Larry L, Polak Julia M
Tissue Engineering and Regenerative Medicine (TERM) Centre, Imperial College Faculty of Medicine, Chelsea and Westminster Campus, 369 Fulham Road, London SW10 9NH, UK.
J Biomed Mater Res B Appl Biomater. 2006 May;77(2):431-46. doi: 10.1002/jbm.b.30455.
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.
生物活性玻璃浸入培养基后会溶解，将其组成离子释放到溶液中。有证据表明，这些离子溶解产物会影响成骨细胞特异性过程。在此，我们研究了58S溶胶-凝胶衍生生物活性玻璃（60摩尔%二氧化硅、36摩尔%氧化钙、4摩尔%五氧化二磷）溶解产物对源自人胎儿长骨外植体培养物（hFOB）的原代成骨细胞的影响。我们使用U133A人类基因组基因芯片寡核苷酸阵列检测22,283个转录本和变体，这些代表了超过18,000个有充分证据的人类基因。源自hFOB单层培养物的样本（生物素化cRNA）与阵列杂交显示，这些细胞高可信度地表达了10,571个转录本。这些包括代表成骨细胞相关基因的转录本，这些基因编码生长因子及其相关分子或受体、细胞外基质（ECM）的蛋白质成分、参与ECM降解的酶、转录因子以及其他重要的成骨细胞相关标志物。用溶胶-凝胶58S溶解的单一剂量离子产物进行24小时处理诱导了许多基因的差异表达，包括IL-6信号转导子/gp130、ISGF-3/STAT1、HIF-1反应性RTP801、ERK1 p44 MAPK（MAPK3）、MAPKAPK2、IGF-I和IGFBP-5。通过实时RT-PCR分析证实了gp130和MAPK3的上调超过2倍以及IGF-I的下调。这些数据表明，58S离子溶解产物可能通过IGF系统和MAPK信号通路的成分介导58S的生物活性作用。
