Osteoclast (Oc) differentiation is fundamentally controlled by receptor activator of nuclear factor kappaB ligand (RANKL). RANKL signalling targets include mitogen-activated protein kinases (MAPKs), nuclear factor kappaB (NF-jB), and nuclear factor of activated T cells (NFAT)c1. In this study, we found that p38 MAPK upstream components transforming growth factor-beta-activated kinase 1 (TAK1), MKK3, and MKK6 increased by RANKL in an early stage of osteoclastogenesis from primary bone marrow cells, which led to enhanced p38 activation. Retroviral transduction of dominant-negative (DN) forms of TAK1 and MKK6, but not that of MKK3, reduced Oc differentiation. Transduction of TAK1-DN and MKK6-DN and treatment with the p38 inhibitor SB203580 attenuated NFATc1 induction by RANKL. TAK1-DN, MKK6-DN, and SB203580, but not MKK3-DN, also suppressed RANKL stimulation of NF-jB transcription activity in a manner dependent on p65 phosphorylation on Ser-536. These results indicate that TAK1 and MKK6 constitute the p38 signalling pathway to participate to Oc differentiation by RANKL through p65 phosphorylation and NFATc1 induction, and that MKK6 and MKK3 have differential roles in osteoclastogenesis from bone marrow precursors.
A novel anion exchange membrane of imidazolium functionalized bisphenol polycarbonate was prepared for application in alkaline fuel cell. Di-imidazolium polycarbonate anionic membrane was synthesized by sequential interfacial polymerization, chloromethylation, substitution with 1-methylimidazole and ion exchange with 1.0 M KOH. Chloromethylation reaction was quantitative to achieve a high content of hydroxide ions. Introduction of conjugated imidazole ring in polymer plays an important role to improve both thermal and chemical stability. Bisphenol polycarbonate is a flexible polymer and shows a good solubility in polar organic solvent. The alkaline imidazolium bisphenol polycarbonate rendered an elevated molecular weight with excellent solubility in polar aprotic solvent. Different levels of substitution and ion exchange were investigated; the resulting membranes showed high ion exchange capacities (IECs) of up to 2.15 mmol g(-1). The imidazolium-functionalized copolymer membranes showed lower water affinity (14.2-42.8% at 30 degrees C) that satisfied an essential criterion for fuel cell application. The chemical structure of the imidazolium functionalized polycarbonate membrane was confirmed by 1H NMR spectroscopy, and also the membrane properties were evaluated by thermogravimetric analysis (TGA) and water uptake (WU), IEC and conductivity assessment. They exhibited hydroxide conductivity above 10(-2) S cm(-1) at room temperature and good chemical stability for up to five days without significant losses of ion conductivity.
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