Hypoxia‐inducible factor 1‐alpha acts as a bridge factor for crosstalk between ERK1/2 and caspases in hypoxia‐induced apoptosis of cementoblasts. Issue 20 (14th September 2021)

• Record Type: Journal Article
• Authors: Yong, Jiawen; von Bremen, Julia; Groeger, Sabine; Ruiz‐Heiland, Gisela; Ruf, Sabine
• Is Part Of: Journal of cellular and molecular medicine. Volume 25:Issue 20(2021)
• Page Start: 9710
• Page End: 9723
• Publication Date: 2021-09-14
• Subjects: adipokines -- apoptosis -- cementoblasts -- cobalt (II) chloride -- hypoxia; Cytology; Medicine; Molecular Biology; Cytologie -- Périodiques; Médecine -- Périodiques; Biologie moléculaire -- Périodiques; Cytology -- Periodicals; Medicine -- Periodicals; Molecular biology -- Periodicals; 611.01805
• DOI: 10.1111/jcmm.16920
• Languages: English
• ISSNs: 1582-1838

Abstract

Abstract: Hypoxia‐induced apoptosis of cementoblasts (OCCM‐30) may be harmful to orthodontic treatment. Hypoxia‐inducible factor 1‐alpha (HIF‐1α) mediates the biological effects during hypoxia. Little is known about the survival mechanism capable to counteract cementoblast apoptosis. We aimed to investigate the potential roles of HIF‐1α, as well as the protein‐protein interactions with ERK1/2, using an in‐vitro model of chemical‐mimicked hypoxia and adipokines. Here, OCCM‐30 were co‐stimulated with resistin, visfatin or ghrelin under CoCl2 ‐mimicked hypoxia. In‐vitro investigations revealed that CoCl2 ‐induced hypoxia triggered activation of caspases, resulting in apoptosis dysfunction in cementoblasts. Resistin, visfatin and ghrelin promoted the phosphorylated ERK1/2 expression in OCCM‐30 cells. Furthermore, these adipokines inhibited hypoxia‐induced apoptosis at different degrees. These effects were reversed by pre‐treatment with ERK inhibitor (FR180204). In cells treated with FR180204, HIF‐1α expression was inhibited despite the presence of three adipokines. Using dominant‐negative mutants of HIF‐1α, we found that siHIF‐1α negatively regulated the caspase ‐ 8, caspase ‐ 9 and caspase ‐ 3 gene expression. We concluded that HIF‐1α acts as a bridge factor in lengthy hypoxia‐induced apoptosis in an ERK1/2‐dependent pathway. Gene expressions of the caspases ‐ 3, caspase ‐ 8 and caspase ‐ 9 were shown to be differentially regulated by adipokines (resistin, visfatin and ghrelin). Our study, therefore, provides evidence for the role of ERK1/2 and HIF‐1α in the apoptotic response of OCCM‐30 cells exposed to CoCl2 ‐mimicked hypoxia, providing potential new possibilities for molecular intervention in obese patients undergoing orthodontic treatment.