Dehydroepiandrosterone improves murine osteoblast growth and bone tissue morphometry via mitogen-activated protein kinase signaling pathway independent of either androgen receptor or estrogen receptor

• DOI: 10.1677/jme.1.02173
• Publication Date: 2007-04-19T13:25:17Z
• Authors: Ling Wang; Yu-Dong Wang; Wen-Jun Wang; Ying Zhu; Da-Jin Li
• Keywords: Mice, Inbred BALB C; 0303 health sciences; Osteoblasts; Bone Density Conservation Agents; Estradiol; MAP Kinase Signaling System; Cell Cycle; Apoptosis; Dehydroepiandrosterone; Bone and Bones; Flutamide; Mice; 03 medical and health sciences; Nitriles; Androgen Receptor Antagonists; Butadienes; Animals; Female; Extracellular Signal-Regulated MAP Kinases; Fulvestrant; Cells, Cultured; Cell Proliferation

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.