ABSTRACT
<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>
Subject(s)
Female , Humans , Apoptosis , Butadienes , Pharmacology , Cell Proliferation , Cells, Cultured , Dehydroepiandrosterone , Pharmacology , Extracellular Signal-Regulated MAP Kinases , Metabolism , Immunoblotting , Mitogen-Activated Protein Kinases , Metabolism , Nitriles , Pharmacology , Osteoblasts , Cell Biology , Metabolism , Osteoclasts , Cell Biology , Metabolism , Osteoprotegerin , Metabolism , RANK Ligand , Metabolism , Signal TransductionABSTRACT
Objective: According to the theory of traditional Chinese medicine, the effect of cervical stimulation on autonomic nervous system activity in humans was investigated.Methods: Healthy young male volunteers were selected as subjects of the trial. The upper cervical spine (C2-5) was stimulated bilaterally with spinal manipulation, and changes in heart rate and heart rate variability were calculated as measures of effects on autonomic nervous system tone. Results: Thirty healthy young male volunteers were tested. It was found that heart rate decreased (R-R interval prolonged) significantly. SDNN and total power spectrum increased significantly, indicating an increase in sympathetic tone. Conclusion: Cervical manipulation can regulate the autonomic nervous system tone in healthy young men, and it suggests a possibility of treating cardiovascular diseases such as arrhythmia with cervical manipulation.