Glucocorticoid transiently upregulates mitochondrial biogenesis in the osteoblast
Journal
Chinese Journal of Physiology
Journal Volume
63
Journal Issue
6
Pages
286-293
Date Issued
2020
Author(s)
Abstract
Glucocorticoid (GC)-induced bone loss is the most prevalent form of secondary osteoporosis. Previous studies demonstrated that long-term incubation of dexamethasone (DEX) induced oxidative stress and mitochondrial dysfunctions, consequently leading to apoptosis of differentiated osteoblasts. This DEX-induced cell death might be the main causes of bone loss. We previously described that DEX induced biphasic mitochondrial alternations. As GC affects mitochondrial physiology through several different possible routes, the short-term and long-term effects of GC treatment on mitochondria in the osteoblast have not been carefully characterized. Here, we examined the expression levels of genes that are associated with mitochondrial functions at several different time points after incubation with DEX. Mitochondrial biogenesis-mediated genes nuclear respiratory factor 1 (Nrf1) and Nrf2 were upregulated after 4-h incubation, and then declined after 24-h incubation, suggesting that mitochondrial biogenesis were transiently upregulated by DEX. In contrast, mitochondrial fusion gene optic atrophy 1 (Opa1) and mitofusin 2 (Mfn2) started to be elevated as the biogenesis started to decrease. Finally, the mitochondrial fission increased and apoptosis becomes prominent. Agree with the mitochondrial biphasic alterations hypothesis, the results suggested an early increase of mitochondrial activities and biogenesis upon DEX stimulation to the osteoblasts. The oxidative phosphorylation and inducible nitric oxide synthase levels increased results in oxidative stress accumulation, leading to mitochondrial fusion, and subsequently fission and triggering the apoptosis. Our results indicated that the primary effects of GC on mitochondria are promoting their functions and biogenesis. Mitochondrial breakdown and the activation of the apoptotic pathways appeared to be the secondary effect after long-term treatment. ? 2020 Wolters Kluwer Medknow Publications. All rights reserved.
Subjects
dexamethasone; inducible nitric oxide synthase; mitofusin 2; transcription factor Nrf1; transcription factor Nrf2; dexamethasone; glucocorticoid; animal cell; apoptosis; Article; controlled study; gene expression; gene fusion; incubation time; long term care; mitochondrial biogenesis; mitochondrial respiration; mitofusin 2 gene; nonhuman; optic atrophy 1 gene; osteoblast; oxidative phosphorylation; oxidative stress; upregulation; metabolism; mitochondrion; organelle biogenesis; Apoptosis; Dexamethasone; Glucocorticoids; Mitochondria; Organelle Biogenesis; Osteoblasts
SDGs
Type
journal article