Effect of glucocorticoid-induced oxidative stress on the expression of Cbfa1.
Glucocorticoids therapy is strongly limited since extended glucocorticoids can cause serious side effects, including increased susceptibility to develop the bone disease osteoporosis. Despite its side effects recognized importance to clinicians, seldom is known about how glucocorticoids directly impact bone-forming osteoblasts. Previous studies showed that dexamethasone (DEX) induces excessive production of reactive oxygen species (ROS), and causes oxidative stress in rat hippocampal slice cultures. To assess the implications and investigate the mechanisms of glucocorticoid-elicited osteoporosis, we hypothesize that DEX exposure induces oxidative stress which leads to decreased Cbfa1 mRNA expression, and predict that the antioxidant N-acetylcysteine (NAC) mitigates the damaging effects of DEX. Oxidative stress is implicated in osteoporosis. Furthermore, the osteoblast transcriptional factor Cbfa1 is reported to play a protective role against osteoporosis in postmenopausal women. Cells treated with (0.1, 1, 10μM) DEX exhibited signs of oxidative damages including depletion in total antioxidant capacity (T-AOC), increased ROS formation, and enhanced lipid peroxidation. Cbfa1 mRNA expression, by RT-PCR, was significantly reduced after exposure to (0.1, 1, 10μM) DEX. Pretreatment with the antioxidant NAC (2mM) prevented DEX-induced decrease in Cbfa1 mRNA. This study provides insight into the underlying mechanisms of high dose DEX-induced osteotoxicity. DEX (0.1, 1, 10μM) decreases the expression of Cbfa1 mRNA and inhibits differentiation and function of osteoblasts by inducing oxidative stress. The antioxidant NAC can mitigate the oxidative stress damaging effects of DEX. In addition, this study distinguishes itself by identifying Cbfa1 as a target for high dose DEX-induced osteotoxicity.
The First Hospital of Lanzhou University, Lanzhou 730000, China.
Yan-Ling
YL
Feng
The First Hospital of Lanzhou University, Lanzhou 730000, China. Electronic address: xulei_tang@126.com.
Xu-Lei
XL
Tang
D000111:Acetylcysteine / Q000494:pharmacology; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002113:Calcification, Physiologic / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics* / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D015675:Osteocalcin / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013194:Staining and Labeling
D050659:Core Binding Factor Alpha 1 Subunit; D005938:Glucocorticoids; D012333:RNA, Messenger; D015675:Osteocalcin; D003907:Dexamethasone; D000469:Alkaline Phosphatase; D000111:Acetylcysteine
Cbfa1; Glucocorticoids; Osteoblasts; Osteoporosis; Oxidative stress