Hypoxia promotes the proliferation of MC3T3-E1 cells via the hypoxia-inducible factor-1α signaling pathway

Investigations into the role of hypoxia have concentrated on hypoxic damage to cells and the associated adaptative mechanisms, however, the effects of hypoxia on cell proliferation and differentiation have received less attention. The present study aimed to investigate the role of hypoxia on the proliferation of MC3T3-E1 cells and examine the molecular mechanism involved. Cells treated with low levels of hypoxia had an increased percentage of S phase cells and a decreased percentage of G1 phase cells, promoted the level of cell proliferation-associated proteins, proliferating cell nuclear antigen and cyclin D. In addition, hypoxia increased cell proliferation by upregulating the expression of hypoxia-inducible factor (HIF)-1 alpha. The phosphoinositide 3-kinase/Akt and mitogen-activated protein kinase/extra-cellular signal-regulated kinase pathways augmented the expression of HIF-1 alpha in the MC3T3-E1 cells. The present study demonstrated that hypoxia induces positive effects on osteoblast proliferation, suggesting a novel strategy in the treatment of osteoporosis.