Activation of Dusp14 protects against osteoclast generation and bone loss by regulating AMPKα-dependent manner.

Osteoporosis is a progressive systematic skeletal disorder featured by decreased bone and enhanced risk of fracture due to an uncoupling of bone resorption. Chronic inflammatory response plays an essential role in osteoporosis progression. Unfortunately, the pathogenesis that contributes to osteoporosis still remains unclear. Dual-specificity phosphatase 14 (Dusp14, also known as MKP6) is a MAP kinase phosphatase, and has important roles in regulating various cellular processes. In the study, we attempted to explore the effects of Dusp14 on osteoporosis development. The results indicated that Dusp14 expression was decreased during osteoclast differentiation and that Dusp14 over-expression markedly alleviated osteoclast generation regulated by macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-κB ligand (RANKL). In M-CSF/RANKL-treated bone marrow-derived cells (BMMs), promoting Dusp14 expression significantly alleviated inflammation and apoptosis by suppressing nuclear factor (NF)-κB and Caspase-3 signaling pathways, respectively. Furthermore, AMP-activated protein kinase (AMPK)-α activation was markedly increased by Dusp14 over-expression in M-CSF/RANKL-incubated BMMs. Importantly, we found that AMPKα blockage obviously abolished the role of Dusp14 in preventing osteoclasts differentiation at least partly via elevating M-CSF/RANKL-elicited inflammation and apoptosis. In vivo, magnesium silicate-induced inflammatory osteoporosis was obviously alleviated in Dusp14 transgenic (TG) mice. Taken together, we defined Dusp14 as an important molecular switch resulting in osteoporosis through an AMPKα-dependent manner.

Video Captioning by Adversarial LSTM.

In this paper, we propose a novel approach to video captioning based on adversarial learning and Long-Short Term Memory (LSTM). With this solution concept we aim at compensating for the deficiencies of LSTM-based video captioning methods that generally show potential to effectively handle temporal nature of video data when generating captions, but that also typically suffer from exponential error accumulation. Specifically, we adopt a standard Generative Adversarial Network (GAN) architecture, characterized by an interplay of two competing processes: a "generator", which generates textual sentences given the visual content of a video, and a "discriminator" which controls the accuracy of the generated sentences. The discriminator acts as an "adversary" towards the generator and with its controlling mechanism helps the generator to become more accurate. For the generator module, we take an existing video captioning concept using LSTM network. For the discriminator, we propose a novel realization specifically tuned for the video captioning problem and taking both the sentences and video features as input. This leads to our proposed LSTM-GAN system architecture, for which we show experimentally to significantly outperform the existing methods on standard public datasets.

[Expression of receptor activator of nuclear factor kappaB ligand and osteoprotegerin of mice osteoblast induced by metal ions].

OBJECTIVE: Lots of metal ions accumulation and over-expression of receptor activator of NF-kappaB ligand (RANKL) around the prosthesis could be found in revision of total hip arthroplasty. To investigate the relationship between metal ions and aseptic loosening by observing the effects of Co2+ and Cr3+ ions on the expression of RANKL and osteoprotegerin (OPG) from osteoblast. METHODS: Osteoblasts were cultured in vitro at the density of 1 x 10(5) cells/mL, and were divided into 2 groups according to different culture solutions. In control group, osteoblasts were cultured with normal medium without CoCl2 and CrCl3. In experimental group, osteoblasts were cultured with the medium including CoCl2 (10 mg/L) and CrCl3 (150 mg/L) solutions. The RT-PCR and ELISA methods were applied to detect the mRNA expression of RANKL and OPG and protein level at 24 and 48 hours after co-cultured, respectively. RESULTS: RT-PCR revealed that the mRNA expression of RANKL and OPG could be found in two groups at 24 and 48 hours after co-cultured, the expression was higher in the experimental group than in control group, especially the expression of RANKL, showing significant difference (P < 0.05). At 24 and 48 hours after co-cultured, the ratios of RANKL mRNA to OPG mRNA in the experimental group were 0.860 and 1.232, respectively, which were significantly higher than those in the control group (0.695 and 0.688, P < 0.05). ELISA revealed that the protein level of RANKL and OPG in experimental group were significantly higher than those in the control group (P < 0.05). CONCLUSION: Co2+ and Cr3+ can stimulate the mRNA expressions of RANKL, OPG and secretion of those protein from osteoblasts, especially increase of the RANKL, which promotes the formation and activation of osteoblasts and the generation of aseptic loosening.