title: The epithelial sodium channel is involved in dexamethasone-induced osteoblast differentiation and mineralization.
abstract: OBJECTIVE
  Glucocorticoids (GCs) can facilitate bone formation, but prolonged GCs exposure in vivo can lead to osteoporosis. The mechanisms underlying these reciprocal effects have not been elucidated.
  
  
  METHODS
  The epithelial sodium channel (ENaC) is a possible regulator of osteoblast proliferation and differentiation, so we examined whether ENaC was involved in mediating the effects of dexamethasone (Dex) on osteoblast.
  
  
  RESULTS
  Expression of the functional α-ENaC subunit was upregulated by 10(-8)M and 10(-6)M Dex, but decreased by 10(-4)M Dex. Furthermore, Dex had similar dose-dependent effects on the expression of three osteogenic genes, Cbfa1, OPN, and OC, with low concentrations enhancing expression and higher concentrations suppressing expression. The effects of Dex on osteoblast proliferation, differentiation, and mineralization were examined in the presence and absence of the ENaC specific antagonist amiloride. Dex at 10(-8)M and 10(-6)M markedly increased osteoblast proliferation, alkaline phosphatase activity (an index of differentiation), and calcium nodule formation, while 10(-4)M had no effect or suppressed all these responses. Amiloride blocked the Dex-induced, osteoblast differentiation and mineralization but had no effect on osteoblast differentiation and mineralization when applied alone. But such changes did not show in osteoblast proliferation. However, the Dex-induced α-ENaC expression was not blocked by RU486, a GC receptor antagonist.
  
  
  CONCLUSIONS
  These results suggest that changes in ENaC activity may involved in Dex-induced differentiation and mineralization of osteoblast. But the Dex-induced effect on ENaC did not mediated by the GC genomic mechanism in osteoblast at this study.
authors: Center of New Drug Function, School of Life Science and Biopharmacy, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China.
authors: Li
authors: L
authors: Lu
authors: Liang
authors: L
authors: Wu
authors: Huanhuan
authors: H
authors: Jia
authors: Yingbing
authors: Y
authors: Li
authors: Jun
authors: J
authors: Chen
authors: Duorong
authors: D
authors: Xu
authors: Qingnan
authors: Q
authors: Li
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000378:metabolism; D002113:Calcification, Physiologic / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D062686:Epithelial Sodium Channel Blockers / Q000494:pharmacology; D053503:Epithelial Sodium Channels / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D006727:Hormone Antagonists / Q000494:pharmacology; D015735:Mifepristone / Q000494:pharmacology; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D061251:Primary Cell Culture; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D015415:Biomarkers; D050659:Core Binding Factor Alpha 1 Subunit; D062686:Epithelial Sodium Channel Blockers; D053503:Epithelial Sodium Channels; D005938:Glucocorticoids; D006727:Hormone Antagonists; D021122:Protein Subunits; D015735:Mifepristone; D000584:Amiloride; D003907:Dexamethasone; D000469:Alkaline Phosphatase