Dehydroepiandrosterone indirectly inhibits human osteoclastic resorption via activating osteoblastic viability by the MAPK pathway

Yu Dong Wang, Min Fang Tao, Wei Wei Cheng, Xiao Hua Liu, Xiao Ping Wan, Ke Mi Cui

Research output: Contribution to journalArticle

12 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1230-1235
Number of pages6
JournalChinese Medical Journal
Volume125
Issue number7
DOIs
StatePublished - 2012

Keywords

  • Dehydroepiandrosterone
  • MAP kinase signaling pathways
  • Osteoblasts
  • Osteoclast

ASJC Scopus subject areas

  • Medicine(all)

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