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The effects of alkaline pH on the initial adhesion of osteoblasts to titanium surfaces was analyzed by single cell force microscopy (SCFM). In the SCFM measurements, the same cells were used to compare their unspecific adhesion to uncoated titanium with their specific adhesion to collagen coated titanium. When the maximum detachment forces (MDFs) were compared at pH 7.4 and 8.0, only slight differences were found on pure titanium, while the MDFs were significantly increased at collagen coated surfaces at pH 8.0. Effects on the subsequent proliferation and gene expression were investigated in an in vitro model system consisting of an alkalizing polyvinyl alcohol (PVA) matrix and a perforated titanium disc. The sodium hydroxide releasing matrix maintained the medium pH between pH 7.6 and pH 8.4 during the entire experiment. Under these conditions, cell counts were significantly increased with respect to the control system after 7 days in culture. These results were supported by gene expression analyses, which showed an upregulation of proliferation-controlling genes of the EGFR1 and PI3K/AKT pathways after 14 days in culture. The SCFM data were complemented by findings of an intensive regulation of genes known to be associated with focal adhesion such as Itga8 and Tnn.

Keywords: AKT; GH; metzincins; mTOR; prolactin EN AKT GH metzincins mTOR prolactin 77 85 9 06/20/23 20230601 NES 230601 Implications Mouse models have improved our understanding of mammary gland growth and development under the control of endocrine signals. Here, we review how miRNAs differentially expressed during mouse mammary gland growth and development might control IGF system activation, expression, and signaling. This not only indicates the relevance of IGFBP4 and IGF2 in the mammary gland but also may indicate that prolactin signaling is regulated by miRNAs via the control of IGF2 mRNA during mouse mammary gland development as discussed earlier in this review ([5]; [17]). Finally, the effects of regulated miRNAs on the IGF system might not only affect the development and function of the mammary gland in female mice but also have implications for distant tissues (Figure 6). [Extracted from the article]