Journal article

Publication year: 2021

Pages: 9710-9723

Journal: Journal of Cellular and Molecular Medicine

Volume number: 25

Issue number: 20

ISSN: 1582-1838

eISSN: 1582-4934

Open access status: Gold

DOI Link: https://doi.org/10.1111/jcmm.16920

Publisher: Wiley

Abstract: 
Hypoxia-induced apoptosis of cementoblasts (OCCM-30) may be harmful to orthodontic treatment. Hypoxia-inducible factor 1-alpha (HIF-1 alpha) 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-1 alpha, 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-1 alpha expression was inhibited despite the presence of three adipokines. Using dominant-negative mutants of HIF-1 alpha, we found that siHIF-1 alpha negatively regulated the caspase-8, caspase-9 and caspase-3 gene expression. We concluded that HIF-1 alpha 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-1 alpha 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.

Harvard Citation style: Yong, J., von Bremen, J., Groeger, S., Ruiz-Heiland, G. and Ruf, S. (2021) Hypoxia-inducible factor 1-alpha acts as a bridge factor for crosstalk between ERK1/2 and caspases in hypoxia-induced apoptosis of cementoblasts, Journal of Cellular and Molecular Medicine, 25(20), pp. 9710-9723. https://doi.org/10.1111/jcmm.16920

APA Citation style: Yong, J., von Bremen, J., Groeger, S., Ruiz-Heiland, G., & Ruf, S. (2021). Hypoxia-inducible factor 1-alpha acts as a bridge factor for crosstalk between ERK1/2 and caspases in hypoxia-induced apoptosis of cementoblasts. Journal of Cellular and Molecular Medicine. 25(20), 9710-9723. https://doi.org/10.1111/jcmm.16920