Hypoxia regulates PGE(2) release and EP1 receptor expression in osteoblastic cells.
Changes in regional O(2) 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 O(2) tension are unclear. In this study we investigated the effects of low O(2) on activation of the hypoxia response element (HRE), prostaglandin E(2) (PGE(2)) production, PGE(2) receptor (EP) expression and proliferation in MC3T3-E1 osteoblastic cells. Cells were cultured for up to 72 h in 2% O(2) (considered hypoxic), 5% O(2) (in the range of normal O(2) tension in vivo) or 21% O(2) (commonly used for cell culture). Cells cultured in 2% O(2) showed activation of the HRE, increased PGE(2) release, increased EP1 expression, and reduced cell proliferation compared to cells grown at 21% O(2). Similarly, cells cultured in 5% O(2) showed increased expression of EP1 and a trend toward a decrease in proliferation, but no activation of the HRE or increase in PGE(2) levels. Expression of EP2, EP3 and EP4 were not affected by O(2) tension. The differences in EP receptor profile observed in cells grown at 5% compared to 21% O(2) suggest that bone cell phenotype may be altered under routine cell culture conditions. Furthermore, our data suggest that hypoxia-dependent PGE(2) production and EP1 expression in bone cells may play a role in bone remodeling and repair in regions of compromised or damaged bone, where O(2) tension is low.
Lee
Christina M
CM
Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California at Davis, Davis, California 95616, USA.
Genetos
Damian C
DC
You
Zongbing
Z
Yellowley
Clare E
CE
D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D015232:Dinoprostone / Q000378:metabolism*; D005786:Gene Expression Regulation; D000860:Hypoxia; D051379:Mice; D010006:Osteoblasts / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D018078:Receptors, Prostaglandin E / Q000235:genetics / Q000378:metabolism*; D058306:Receptors, Prostaglandin E, EP1 Subtype
C545636:Ptger1 protein, mouse; D018078:Receptors, Prostaglandin E; D058306:Receptors, Prostaglandin E, EP1 Subtype; D015232:Dinoprostone; D010100:Oxygen