Oxygen availability is a
criti
cal signal for proper development of many tissues, however there is limited knowledge of its role in the maturation of bone
cells. To test the hypothesis that low pO
2 regulates bone
cell mineralization, MLO-A5 and MLO-Y4
cells were
cultured in monolayer and three-dimensional alginate s
caffolds in hypoxia (2%O
2) or normoxia (20%O
2). Hypoxia redu
ced mineralization and de
creased alkaline phosphatase a
ctivity of preosteo
cyte-like MLO-A5
cells in both monolayer and alginate
cultures. Similar
changes in osteogeni
c a
ctivity were seen when the were sub
je
cted to
chemi
cal hypoxia. Likewise, Osteo
cyte-like MLO-Y4
cells also exhibited redu
ced osteogeni
c a
ctivity in hypoxia relative to normoxi
c controls. Based on these observations, it is
con
cluded that a low pO
2 de
creased the mineralization potential of bone
cells at both early and late stages of maturation. Sin
ce the oxemi
c state is transdu
ced by the trans
cription fa
ctor, HIF-1
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changes in mineral formation. It was noted that when HIF-1
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ced, mineralization a
ctivities were not restored. Indeed, in hypoxia, in relationship to wild type
controls, the mineralization potential of the kno
ckdown
cells was further redu
ced. Based on these findings, it is
con
cluded that the osteogeni
c a
ctivity of preosteo
cyte-like
cells is dependent on both the O
2 tension and the expression of HIF-1
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