Hypoxia-inducible factor-1α antagonizes the hypoxia-mediated osteoblast cell viability reduction by inhibiting apoptosis

Abstract

Abstract. Bone fracture is accompanied with poor oxygen supply and nutrient deficiency in the local fracture site, and oxygen supply is an important factor that can affect fracture healing. Hypoxia-inducible factor-1 (HIF-1) plays a key role in the regulation of oxygen homeostasis. HIF-1α is rapidly upregulated in response to hypoxia and antagonizes hypoxia-induced apoptosis. In the present study, the viability of an osteoblast cell line, MC3T3-E1, and the expression of HIF-1α protein in the MC3T3-E1 cells was examined under hypoxic conditions. The HIF-1α level was then manipulated and the reduction in the viability of the MC3T3-E1 cells in response to the hypoxia was re-evaluated. In addition, the regulation of HIF-1α in the adaptation of MC3T3-E1 cells to hypoxia was explored. The results showed that the viability of MC3T3-E1 cells decreased and the expression of HIF-1α protein increased under hypoxic conditions. Furthermore, the reduction in the viability of MC3T3-E1 cells post-hypoxia was attenuated by HIF-1α overexpression, while HIF-1α-knockdown by small interfering RNA enhanced the hypoxia-induced decrease in cell viability. It was additionally found that the forced expression of HIF-1α inhibited the hypoxia-induced cell apoptosis. These findings indicate that the forced expression of HIF-1α inhibits hypoxia-induced apoptosis and thus attenuates the hypoxia-induced decrease in cell viability.

Programmed cell death of periodontal ligament cells

“…Under hypoxia, HIF‐1α rapidly upregulates and combats hypoxia‐induced apoptosis of osteoblasts (Xu et al, 2015). Additionally, both HIF‐1α and HIF‐2α have been found to have protective effects in oxidative stress.…”

Gastric Mucosal Lesions in Tibetans with High-Altitude Polycythemia Show Increased HIF-1A Expression and ROS Production

“…Hypoxia-inducible factor-1 (HIF-1) is a transcription factor, consisting of α and β heterodimer subunits, and is coded by the HIF-1A gene. HIF-1A acts as the main regulator of homeostasis in hypoxic cells by activating the transcription of various genes, including those involved in energy metabolism [8, 9], angiogenesis [10, 11], and apoptosis [12, 13], as well as other genes involved in increasing oxygen delivery or promoting metabolism under hypoxic conditions [14, 15]. Therefore, HIF-1A plays an important role in the pathophysiology of ischemic diseases [16, 17].…”