ABSTRACT
<p><b>AIM</b>To investigate the effect of ginkgolide B on the proliferation of VSMC and the secretion of chemokines by U937 cells stimulated by oxLDL or PAF. In addition, to analyze whether the effect of oxLDL is mediated through PAF receptor.</p><p><b>METHODS</b>Using 3H-Tdr incorporation assay, the proliferation of VSMC was measured. The protein and mRNA level of MCP-1 and IL-8 in U937 cells were determined by RT-PCR and ELISA. Using Western blotting the p65 and IkappaB was quantified. The binding of oxLDL to U937 cell was measured by a radio-ligand binding assay of 3H-PAF.</p><p><b>RESULTS</b>Ginkgolide B inhibited, in dose-dependent manner, the proliferation of VSMC and the secretion of chemokines by U937 cells stimulated by oxLDL, and inhibited the oxLDL-induced p65 activation and depletion of IKappaB. oxLDL inhibited PAF binding to U937 cells.</p><p><b>CONCLUSION</b>Ginkgolide B, as a PAF antagonist, possesses the effect of inhibiting the proliferation of VSMC and the secretion of chemokines by U937 cells stimulated by oxLDL in vitro. The effect of oxLDL is, at least in part, mediated through PAF receptor.</p>
Subject(s)
Animals , Humans , Male , Rats , Aorta, Thoracic , Cell Biology , Cell Proliferation , Cells, Cultured , Chemokine CCL2 , Genetics , Diterpenes , Pharmacology , Dose-Response Relationship, Drug , Ginkgo biloba , Chemistry , Ginkgolides , I-kappa B Proteins , Metabolism , Interleukin-8 , Genetics , Lactones , Pharmacology , Lipoproteins, LDL , Pharmacology , Muscle, Smooth, Vascular , Cell Biology , Myocytes, Smooth Muscle , Metabolism , Plants, Medicinal , Chemistry , Platelet Activating Factor , RNA, Messenger , Genetics , Rats, Wistar , Synaptotagmin I , Metabolism , U937 CellsABSTRACT
<p><b>AIM</b>To study the inhibitory action of diacerein on the formation of osteoclasts (OCLs) and their activity in bone resorption as well as the relationship between this action and the expression of osteoprotegerin (OPG) and receptor activator of NF-kappaB ligand (RANKL) in MC3T3-E1 cells.</p><p><b>METHODS</b>A coculture system constituted with MC3T3-E1 cells and bone marrow cells for osteoclasts formation was established in vitro. TRAP-positive and multinucleated cells with three or more nuclei in each cell were counted as osteoclasts and the number of pits formed on the dentine slices was determined to judge the activity of osteoclasts. Western blotting, RT-PCR and flow cytometer were used to detect the expression of OPG and RANKL in MC3T3-E1 cells.</p><p><b>RESULTS</b>Diacerein significantly inhibited the formation and function of the cultured osteoclasts stimulated by IL-1beta. sRANKL could reverse the effect of diacerein. Diacerein inhibited protein and mRNA expression of RANKL but enhanced those of OPG in MC3T3-E1 cells.</p><p><b>CONCLUSION</b>Diacerein may inhibit osteoclastic bone destruction through the inhibition of RANKL expression and the increase of OPG expression in MC3T3-E1 cells.</p>