Abnormally increased resorption contributes to bone degenerative diseases such as Paget’s disease of bone (PDB) through unclear mechanisms. Recently, the optineurin (OPTN) gene has been implicated in PDB, and global OPTN knockout mice (Optn−/−) were shown to exhibit increased formation of osteoclasts (osteoclastogenesis). Growing evidence, including our own, has demonstrated that intracellular reactive oxygen species (ROS) stimulated by receptor activator of nuclear factor kappa-B ligand (RANKL) can act as signaling molecules to promote osteoclastogenesis. Here, we report that OPTN interacts with nuclear factor erythroid-derived factor 2-related factor 2 (NRF2), the master regulator of the antioxidant response, defining a pathway through which RANKL-induced ROS could be regulated for osteoclastogenesis. In this study, monocytes from Optn−/− and wild-type (Optn+/+) mice were utilized to differentiate into osteoclasts, and both qRT-PCR and tartrate-resistant acid phosphatase (TRAP) staining showed that the Optn−/− monocytes exhibited enhanced osteoclastogenesis compared to the Optn+/+ cells. CellROX® staining, qRT-PCR, and Western blotting indicated that OPTN deficiency reduced the basal expression of Nrf2, inhibited the expression of NRF2-responsive antioxidants, and increased basal and RANKL-induced intracellular ROS levels, leading to enhanced osteoclastogenesis. Coimmunoprecipitation (co-IP) showed direct interaction, and immunofluorescence staining showed perinuclear colocalization of the OPTN-NRF2 granular structures during differentiation. Finally, curcumin and the other NRF2 activators attenuated the hyperactive osteoclastogenesis induced by OPTN deficiency. Collectively, our findings reveal a novel OPTN-mediated mechanism for regulating the NRF2-mediated antioxidant response in osteoclasts and extend the therapeutic potential of OPTN in the aging process resulting from ROS-triggered oxidative stress, which is associated with PDB and many other degenerative diseases.Subject terms: Mechanisms of disease, Stress signalling相似文献
The photoisomerization mechanism of the neutral form of the photoactive yellow protein (PYP) chromophore is investigated using ab initio quantum chemistry and first-principles nonadiabatic molecular dynamics (ab initio multiple spawning or AIMS). We identify the nature of the two lowest-lying excited states, characterize the short-time behavior of molecules excited directly to S2, and explain the origin of the experimentally observed wavelength-dependent photoisomerization quantum yield. 相似文献
A new chelating fiber, poly(acrylo‐amidino diethylenediamine), was synthesized based on polyacrylonitrile fibers in diethylenetriamine with the aid of AlCl3. Complex formation with CrO42– was strongly pH‐dependent, as complexes formed only in the presence of NH3+ and NH2+. In the medium pH region, both ionic and hydrogen bonds were formed between poly(acrylo‐amidino diethylenediamine) and the chromate ion, as was confirmed by means of FT‐IR spectroscopy. 相似文献
Nickel-ruthenium alloys with various compositions have been deposited by electrodeposition for the first time. Cyclic voltammetry and linear stripping voltammetry measurements show that codeposition of nickel with ruthenium is possible below the potential value of nickel reduction. High-quality alloys containing nickel and ruthenium can be plated at cathodic potentials ranging from − 0.5 to − 1.0 V vs SCE. Deposited coatings were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), and atomic force microscopy (AFM). The diffractograms obtained show that an increase of nickel concentration in alloy will lead to a change in the phase composition and formation of NiRu (100) and (101) phases which is observed to be 78 mas.% Ni. SEM studies confirm the surface homogeneity and presence of small, regular grains. AFM observation allows the estimation of the real surface area of obtained alloys which increase with more negative electrodeposition potentials. Ni-Ru alloys were found to be highly electroactive in the water splitting process, which can be connected with the presence of the NiRu phase and a well-developed electroactive area.
A series of photochromic spirooxazine-containing zinc(II) diimine bis-thiolate complexes were successfully synthesized, and their photophysical and photochromic properties were studied. The X-ray crystal structure of complex 1a has also been determined. Upon excitation by UV light at 330 nm, all the ligands and complexes exhibit photochromic behavior. The thermal bleaching kinetics of the ligands and the complexes were studied in dimethylformamide at various temperatures. The photochemical quantum yields for the photochromic reactions of the ligands and complexes were also determined. 相似文献
A novel series of blue emitting silylene-spaced diphenylanthracene derivatives have been synthesized and characterized. The rhodium-catalyzed hydrosilylation of bis[4-(dimethylsilyl)phenyl]anthracene 3-4 yielded stable 9,10-disubstituted (E)-divinylsilylene-diphenylanthracene products 7-10 and salt elimination reaction of bis[4-(chlorodimethylsilyl)phenyl]anthracene 5-6 gave 9,10-disubstituted disilyldiphenylanthracene compounds 11-14. They are fluorescent in the blue region with good quantum efficiencies. The rhodium-catalyzed polyaddition including 2-tert-butyl-9,10-bis[4-(dimethylsilyl)phenyl]anthracene (4) afforded the nonconjugated copolymer 15. 相似文献
A new branched-pore adsorption model has been developed using an external mass transfer coefficient, Kf, an effective diffusivity, Deff, a lumped micropore diffusion rate parameter, Kb, and the fraction of macropores, f, to describe sorption kinetic data from initial adsorbent-adsorbate contact to the long-term adsorption phase. This model has been applied to an environmental pollution problem—the removal of two dyes, Acid Blue 80 (AB80) and Acid Red 114 (AR114), by sorption on activated carbon. A computer program has been used to generate theoretical concentration-time curves and the four mass transfer kinetic parameters adjusted so that the model achieves a close fit to the experimental data. The best fit values of the parameters have been determined for different initial dye concentrations and carbon masses. Since the model is specifically applicable to fixed constant values of these four parameters, a further and key application of this project is to see if single constant values of these parameters can be used to describe all the experimental concentration-time decay curves for one dye-carbon system.The error analysis and best fit approach to modeling the decay curves for both dye systems show that the correlation between experimental and theoretical data is good for the fixed values of the four fitted parameters. A significantly better fit of the model predictions is obtained when Kf, Kb and f are maintained constant but Deff is varied. This indicates that the surface diffusivity may vary as a function of surface coverage. 相似文献