OXYGEN TENSION REGULATES PREOSTEOCYTE MATURATION AND MINERALIZATION

摘要

The goal of this investigation was to test the hypothesis that low pO2 regulates bone cell mineralization. MLO-A5 and MLO-Y4 cells were cultured in monolayer and alginate scaffolds in hypoxia (2% O2) or normoxia (20% O2). Reduction of the O2 tension from 20% to 2% resulted in reduced mineralization and decreased alkaline phosphatase activity of MLO-A5 cells in both monolayer and three-dimensional cultures. Similar changes in osteogenic activity were seen when these preosteocyte-like cells were subjected to chemical hypoxia. Likewise, in hypoxia, osteocyte-like MLO-Y4 cells exhibited reduced osteogenic activity when compared to normoxic controls. Based on these observations, it is concluded that a low pO2 lowered the mineralization potential of bone cells at both early and late stages of maturation. Since the oxemic state is transduced by the transcription factor, HIF-1α, experiments were performed to determine if this protein was responsible for the observed changes in mineral formation. It was noted that when HIF-1α was silenced, mineralization activities were not restored. Indeed, in hypoxia, in relationship to wild type controls, the mineralization potential of the knockdown cells was further reduced. Based on these findings, it is concluded that the osteogenic activity of preosteocyte-like cells is dependent on both the O2 tension and the expression of HIF-1α.