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The W9 peptide has been shown to act as a receptor activator for nuclear factor-κB ligand (RANKL) antagonist and tumor necrosis factor (TNF)-α antagonist, which can promote bone formation and inhibit bone resorption. Studies on the W9 peptide at the cellular level have mainly focused on osteoblasts, and little research on the mechanism by which the W9 peptide regulates osteoclasts has been reported, which was the aim of this work. In this study, a rat mandibular defect model was established in vivo and implanted with hydrogel containing the W9 peptide for 2 weeks and 4 weeks, and histochemical staining was used to evaluate the formation of new bone and the changes in osteoclasts. RAW264.7 cells were cultured in vitro for osteoclast induction, and different concentrations of W9 peptide were added. Tartrate resistant acid phosphatase staining, monodansylcadaverine staining, TdT-mediated dUTP Nick-End Labeling assay, real-time PCR and Western blot were used to detect osteoclast differentiation, autophagy and apoptosis. Our results showed that the W9 peptide could reduce osteoclastogenesis and osteoclast activity induced by RANKL, and these effects were partly due to the inhibition of osteoclast autophagy. On the other hand, the W9 peptide could promote mature osteoclast apoptosis, in which autophagy might play an antagonistic role. Taken together, these results suggest that the W9 peptide inhibits osteoclastogenesis and osteoclast activity by downregulating osteoclast autophagy and promoting osteoclast apoptosis. Our results will benefit the development and application of new small molecule peptides for the treatment of bone resorption diseases. [ABSTRACT FROM AUTHOR]

The apoptosis of mature osteocytes is the main factor causing damage to the microstructure of cortical bone in glucocorticoid-induced osteoporosis (GIOP). Our previous research found damaged areas and empty osteocytes lacunae in the tibial cortical bone of GIOP mice. However, the specific mechanism has not been clarified. Recently, a study showed that the quality of the cortical bone significantly increased by knocking out Notum, a gene encoding α/β hydrolase. However, it is not clear whether Notum affects cortical bone remodeling by participating in glucocorticoids (GCs)-induced apoptosis of osteocytes. The present study aimed to explore the correlation between Notum, osteocytes apoptosis, and cortical bone quality in GIOP. Prednisolone acetate was intragastrically administered to mice for two weeks. Histochemical staining was applied to evaluate changes in GIOP and Notum expression. Osteocytes were stimulated with prednisolone, and cell viability was assessed via CCK8. Hoechst 33342/PI staining, flow cytometry, RT-PCR, and western blot were used to detect osteocytes apoptosis, siRNA transfection efficiency, and expressions of pathway related factors. The results showed that the number of empty osteocytes lacunae increased in GIOP mice. TUNEL-stained apoptotic osteocytes and Notum immuno-positive osteocytes were also observed. Furthermore, prednisolone was found to promote Notum expression and osteocytes apoptosis in vitro. Knocking down Notum via siRNA partially restored osteocytes apoptosis and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/glycogen synthase kinase-3β (GSK3β)/β-catenin pathway. These findings showed GCs-induced osteocytes apoptosis by promoting Notum expression and inhibiting PI3K/AKT/GSK3β/β-catenin pathway. Thus, Notum might be a potential therapeutic target for the treatment of GIOP. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic, progressive, and systemic inflammatory joint disease characterized by synovial inflammation and joint damage. Abnormal activation of fibroblast-like synoviocytes is an initial event of synovial inflammation and joint damage, which can significantly aggravate the progression of RA. Clinical studies have shown that synovitis may be associated with pyroptosis. Therefore, this study is mainly aim for exploring the underlying mechanisms of relationship between inflammation and pyroptosis during synovitis. A cell model of synovitis was constructed by stimulating synovial fibroblasts RSC-364 cells with lipopolysaccharide (LPS). In vitro, we found that LPS can induce pyroptosis of synovial fibroblasts through NOD-like receptor pyrin domain-3/caspase-1/gasdermin D and caspase-3/gasdermin E two signaling pathways, and these two signaling pathways can promote each other. In addition, NF-κB signaling pathway, as the upstream of these two pathways, is involved in regulating the pyroptosis of synovial fibroblast. These results suggest that pyroptosis may be triggered during the occurrence of RA. We hope to provide a new perspective for the study of RA and a new therapeutic target for clinical treatment of RA. [ABSTRACT FROM AUTHOR]

This paper presents a distributed adaptive neural tracking consensus control strategy for a class of stochastic nonlinear multiagent systems with whole state time delays, input and output constrains. The considered systems are involved in the existence of whole state delays and stochastic disturbances, which makes the controller design more difficult and complex. Firstly, time delays are related to unknown dynamic interactions with the whole states of the agent systems, and novel Lyapunov-Krasovskii functionals are constructed. Secondly, the smooth asymmetric saturation nonlinearity is given based on Gaussian error function, output constraints are achieved via barrier Lyapunov functions, and neural networks are utilized to deal with the completely unknown nonlinearities and stochastic disturbances. Then, based on Lyapunov stability theory, a delay-independent adaptive controller is developed via Lyapunov-Krasovskii functionals and backstepping technique, and it reduces the complexity of learning parameters. It is proved that the proposed approximation-based controller can guarantee that all closed-loop signals are cooperatively semi-globally uniformly ultimately bounded (CSGUUB), and the tracking errors between the followers and the leaders eventually converge to a small neighbourhood around the origin. Finally, simulation studies are carried out, and the simulation results verify the correctness and effectiveness of the proposed strategy. [ABSTRACT FROM AUTHOR]

Periodontitis is characterized by alveolar bone destruction and is one of the most common chronic oral diseases. Inflammatory cytokines released by pyroptosis, which can be triggered by oxidative stress, are critical in the development of periodontitis. This study aims to clarify whether oxidative stress causes osteoblast dysfunction by inducing pyroptosis in the process of periodontitis. We found that treatment with lipopolysaccharide (LPS) led to NLRP3 inflammasome-mediated pyroptosis of MG63 cells as well as decreased cell migration. Of note, LPS stimulation increased LDH release in a time- and dose-dependent manner. However, inhibition of reactive oxygen species with N-acetyl-L-cysteine attenuated oxidative stress-mediated pyroptosis and improved migration injury in osteoblasts treated with LPS. Further, inhibition of the NLRP3 inflammasome with MCC950 improved osteoblast migration and restored the expression of osteogenic differentiation-related proteins such as COL 1, RUNX 2 and ALP. In conclusion, oxidative stress caused by LPS induces pyroptosis in osteoblasts, leading to osteogenic dysfunction. [ABSTRACT FROM AUTHOR]

HVDC auxiliary emergency power control can improve the transient stability of AC/DC power system. Compared with other control methods, HVDC auxiliary emergency power control has the advantages of quick response, large adjustment capacity and less investment, so it is the primary choice to improve the transient stability. Taking multi-infeed DC (MIDC) transmission system as the research object, based on the definition of the traditional power support factor, considering the influence of the electrical connection of the sending-end power grid on the power support, a new power support factor (NPSF) is defined. Based on the NPSF, multiple DC coordination sharing strategies are implemented when one of the DC faults occurs. Finally, MIDC is built on the PSCAD. Single DC auxiliary power control and multiple DC auxiliary power coordinated control were simulated, respectively. Rationality of the definition of NPSF is verified, and it is concluded that multiple DC joint power control is superior to single DC. [ABSTRACT FROM AUTHOR]