Abstract
Long‐term or heavy use of glucocorticoids can cause severe necrosis of the femoral head, but the underlying mechanisms are still unclear. Recent studies have found that mitochondrial dynamics play an important role in femoral head necrosis. Here, we investigated the effect of dexamethasone on the mitochondrial function of mesenchymal stem cells. We observed that high concentrations of dexamethasone (10−6 mol·L−1) decreased cell activity, promoted apoptosis, elevated levels of reactive oxygen species and disrupted mitochondrial dynamics. Furthermore, dexamethasone (10−6 mol·L−1) inhibited osteogenesis of stem cells and promoted adipogenesis. These findings may facilitate greater understanding of the adverse effects of dexamethasone on the femoral head.
Highlights
Long-term or heavy use of glucocorticoids can cause severe necrosis of the femoral head, but the underlying mechanisms are still unclear
It was clear that the high concentration of dexamethasone (10À6 molÁLÀ1) inhibits the proliferation of mesenchymal stem cell (MSC), lower concentrations of dexamethasone promoted MSC proliferation (P < 0.05) after 5 days, and there is no statistical difference between the control group and experimental group after 1 and 3 days
A current study found that glucocorticoid treatment can decrease osteogenesis and increase adipogenesis, because both osteogenesis and adipogenesis begin in the bone marrow precursor cells [25]
Summary
Long-term or heavy use of glucocorticoids can cause severe necrosis of the femoral head, but the underlying mechanisms are still unclear. Recent studies have found that mitochondrial dynamics play an important role in femoral head necrosis. We observed that high concentrations of dexamethasone (10À6 molÁLÀ1) decreased cell activity, promoted apoptosis, elevated levels of reactive oxygen species and disrupted mitochondrial dynamics. Dexamethasone (10À6 molÁLÀ1) inhibited osteogenesis of stem cells and promoted adipogenesis These findings may facilitate greater understanding of the adverse effects of dexamethasone on the femoral head. Abbreviations ALP, alkaline phosphatase; C-caspase-3, cleaved caspase-3; CCK-8, Cell Counting Kit-8; Cyt-c, cytochrome c; Fis, fission 1; HLA, human leukocyte antigen; MFF, mitochondrial fission factor; Mfn, mitofusin; MSC, mesenchymal stem cell; ONFH, osteonecrosis of the femoral head; PI, propidium iodide; ROS, reactive oxygen species; Sal B, salvianolic acid B; SD, standard deviation; SIRT, sirtuin; WB, western blotting. Dexamethasone disrupts mitochondrial dynamics of MSC kinetic imbalance and the ROS level increase induced by it play important roles in this process. SIRT3 plays an important role in cell synthesis of nicotinamide adenine dinucleotide+, ATP and mitochondrial respiratory cycle, and is of great significance for the mitochondrial respiratory chain and antioxidant system [13,14,15,16]
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