Dehydroepiandrosterone improves murine osteoblast growth and bone tissue morphometry via mitogen-activated protein kinase signaling pathway independent of either androgen receptor or estrogen receptor.
Dehydroepiandrosterone (DHEA) may be a promising agent for postmenopausal osteoporosis (PMO), but its mechanism to modulate osteoblasts (OBs) is yet to be explained. To elucidate the effects of DHEA treatment on the ovariectomized (OVX) mice and its mechanisms, we evaluated the morphology of mice bone tissue and expression of proliferating cell nuclear antigen (PCNA) in the vertebrae-derived OB after having treated the OVX animals with DHEA. The results showed that DHEA administration increased the expression of PCNA in OB and changed the bone tissue morphometry of the PMO model. To further investigate this mechanism, the OB was isolated from neonatal mice calvariae by the enzyme-digested assay, exposed to DHEA, and then analyzed for ultrastructure, DNA content, early apoptotic cells, and phosphorylation of extracellular signal-regulated kinase 1/2. It was found that DHEA promoted proliferation and inhibited apoptosis of OB significantly, via mitogen-activated protein kinase signaling pathway independent of either androgen receptor or estrogen receptor, suggesting that it may exert roles via a DHEA-specific receptor directly, not by way of conversion to androgens or estrogens.
Wang
Ling
L
Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, China.
Wang
Yu-Dong
YD
Wang
Wen-Jun
WJ
Zhu
Ying
Y
Li
Da-Jin
DJ
D059002:Androgen Receptor Antagonists; D000818:Animals; D017209:Apoptosis; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D001842:Bone and Bones / Q000166:cytology / Q000187:drug effects*; D002070:Butadienes / Q000494:pharmacology; D002453:Cell Cycle; D049109:Cell Proliferation; D002478:Cells, Cultured; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D005485:Flutamide / Q000494:pharmacology; D000077267:Fulvestrant; D020935:MAP Kinase Signaling System / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009570:Nitriles / Q000494:pharmacology; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D010052:Ovariectomy; D010766:Phosphorylation; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011944:Receptors, Androgen / Q000502:physiology*; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000502:physiology*
D059002:Androgen Receptor Antagonists; D050071:Bone Density Conservation Agents; D002070:Butadienes; D009570:Nitriles; D018809:Proliferating Cell Nuclear Antigen; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; C113580:U 0126; D000077267:Fulvestrant; D003687:Dehydroepiandrosterone; D004958:Estradiol; D005485:Flutamide; D048049:Extracellular Signal-Regulated MAP Kinases