title: Dehydroepiandrosterone indirectly inhibits human osteoclastic resorption via activating osteoblastic viability by the MAPK pathway.
abstract: BACKGROUND
  Dehydroepiandrosterone (DHEA) is widely known for its beneficial effect on postmenopausal osteoporosis, although the underlying mechanisms remain mainly unclear. In this study, we tried to determine the activation of mitogen-activated protein kinase signal pathways during DHEA treatment and the indirect role of osteoblasts (OBs) on osteoclasts under the DHEA treatment of postmenopausal osteoporosis.
  
  
  METHODS
  Primary human OBs and osteoclast-like cells were cultured and, we pretreated OBs with or without U0126 (a highly selective inhibitor of both MEK1 and MEK2). The OBs were treated with DHEA. We then tested the effects of DHEA on human osteoblastic viability, osteoprotegerin production and the expression of phosphor-ERK1/2 (extracellular signal-regulated kinase). In the presence or absence of OBs, the function of osteoclastic resorption upon DHEA treatment was calculated.
  
  
  RESULTS
  DHEA promoted the human osteoblastic proliferation and inhibited the osteoblastic apoptosis within the concentration range of 10(-8) - 10(-6) mol/L (P < 0.05, P < 0.01, respectively). Within the effective concentration range, the expression of phosphor-ERK1/2 and osteoprotegerin was increased by DHEA and blocked by U0126. In the presence of OBs, DHEA could significantly decrease the number and the area of bone resorption lacuna (P < 0.05 and P < 0.01, respectively). Without OBs, however, the effects of DHEA on the bone resorption lacuna were almost completely abolished.
  
  
  CONCLUSIONS
  DHEA could indirectly inhibit the human osteoclastic resorption through promoting the osteoblastic viability and osteoprotegerin production, which is mediated by mitogen-activated protein kinases signal pathway involving the phosphor-ERK1/2.
authors.affiliation: Department of Gynecology, International Peace Maternal and Child Health Hospital, Shanghai Jiao Tong University, Shanghai, China. owangyudong@hotmail.com
authors.forename: Yu-dong
authors.initials: YD
authors.lastname: Wang
authors.forename: Min-fang
authors.initials: MF
authors.lastname: Tao
authors.forename: Wei-wei
authors.initials: WW
authors.lastname: Cheng
authors.forename: Xiao-hua
authors.initials: XH
authors.lastname: Liu
authors.forename: Xiao-ping
authors.initials: XP
authors.lastname: Wan
authors.forename: KeMi
authors.initials: K
authors.lastname: Cui
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002070:Butadienes / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D015151:Immunoblotting; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D053244:Osteoprotegerin / Q000378:metabolism; D053245:RANK Ligand / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D002070:Butadienes; D009570:Nitriles; D053244:Osteoprotegerin; D053245:RANK Ligand; C113580:U 0126; D003687:Dehydroepiandrosterone; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases