Hypoxia regulates PGE2 release and EP1 receptor expression in osteoblastic cells

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Abstract
Changes in regional O2 tension that occur during fracture and skeletal unloading may stimulate local bone cell activity and ultimately regulate bone maintenance and repair. The mechanisms by which bone cells sense and respond to changes in O2 tension are unclear. In this study we investigated the effects of low O2 on activation of the hypoxia response element (HRE), prostaglandin E2 (PGE2) production, PGE2 receptor (EP) expression and proliferation in MC3T3‐E1 osteoblastic cells. Cells were cultured for up to 72 h in 2% O2 (considered hypoxic), 5% O2 (in the range of normal O2 tension in vivo) or 21% O2 (commonly used for cell culture). Cells cultured in 2% O2 showed activation of the HRE, increased PGE2 release, increased EP1 expression, and reduced cell proliferation compared to cells grown at 21% O2. Similarly, cells cultured in 5% O2 showed increased expression of EP1 and a trend toward a decrease in proliferation, but no activation of the HRE or increase in PGE2 levels. Expression of EP2, EP3 and EP4 were not affected by O2 tension. The differences in EP receptor profile observed in cells grown at 5% compared to 21% O2 suggest that bone cell phenotype may be altered under routine cell culture conditions. Furthermore, our data suggest that hypoxia‐dependent PGE2 production and EP1 expression in bone cells may play a role in bone remodeling and repair in regions of compromised or damaged bone, where O2 tension is low. J. Cell. Physiol. 212: 182–188, 2007.

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