Mengdan Zhong

osteoclast differentiation, hydroxyapatite resorption activity, and expression of osteoclastogenesis-related genes, such as NFATc1, MMP9, CTSK, Acp5 and c-Fos, in RANKL-induced bone marrow macrophages (BMMs) and RAW264.7 cells. It also reduced intracellular ROS levels by suppressing expression of TRAF6 and NADPH oxidase 1 (NOX1) and increasing expression of antioxidant enzymes such as heme oxygenase-1 (HO-1). Puerarin inhibited TRAF6/ROS-dependent activation of the MAPK and NF-κB signaling pathways in RANKL-induced RAW264.7 cells, and these effects were partially reversed by HO-1 silencing or TRAF6 overexpression. These findings suggest puerarin alleviates loss of bone mass in the OVX-model mice by suppressing osteoclastogenesis via inhibition of the TRAF6/ROS-dependent MAPK/NF-κB signaling pathway.

T cells and decreasing regulatory T cells in the tumor while increasing effector memory T cells in the spleen. Overall, our platform demonstrates that CCMP@R837 can be a potential candidate for preventive cancer vaccines in the clinic.

BACKGROUND: Recent studies suggest that there is a link between the gut microbiota and glucose metabolism. This study aimed to compare the gut microbiota during early pregnancy of women with hyperglycymia to those with normal blood glucose. METHODS: Gut microbial composition was analysed in 22 women with hyperglycaemia and 28 age-matched healthy controls during their first prenatal visits (< 20 weeks) using high throughput sequencing of the V3-V4 region of the 16S ribosomal RNA gene. Hyperglycemia was diagnosed based on the criteria recommended by the International Association of Diabetes and Pregnancy Study Groups in 2010. RESULTS: Women with hyperglycemia in pregnancy (HIP) had significantly lower microbial richness and diversity compared with healthy pregnant women. The proportions of the Firmicutes and Bacteroidetes phyla and the ratio of Firmicutes:Bacteroidetes were not different between the two groups. We observed that individuals with HIP had an increased abundance of Nocardiaceae, Fusobacteriaceae, etc., whereas healthy controls had significantly higher levels of Christensenellaceae, Clostridiales_vadinBB60_group, Coriobacteriaceae, etc. Similarly, levels of the members of the Ruminococcaceae family, including Ruminococcaceae_UCG-014, Ruminococcaceae_UCG-003, and Ruminococcaceae_UCG-002, were significantly reduced in the HIP group and were negatively correlated with HbA1c. HbA1c levels were positively correlated with Bacteroidaceae and Enterobacteriaceae and negatively correlated with Christensenellaceae, etc. CRP was positively correlated with the Bacteroidaceae and Fusobacteriaceae families and the Fusobacterium genus. CONCLUSIONS: Our study revealed that individuals with HIP have gut microbial dysbiosis and that certain bacterial groups are associated with glucose metabolism during pregnancy. Further study is needed to provide new ideas to control glucose by modifying the gut microbiota.

BACKGROUND: The inhibition of osteogenic differentiation is a major factor in glucocorticoid-induced bone loss, but there is currently no effective treatment. Dopamine, a major neurotransmitter, transmits signals via five different seven-transmembrane G protein-coupled receptors termed D1 to D5. Although the relevance of the neuroendocrine system in bone metabolism has emerged, the precise effects of dopamine receptor signaling on osteoblastogenesis remain unknown. METHODS: In vitro, western blotting and immunofluorescence staining were used to observe the expression of dopamine receptors in MC3T3-E1 and BMSCs cells treated with dexamethasone (Dex). In addition, Alizarin red S (ARS) and alkaline phosphatase (ALP) staining and western blotting were used to evaluate the effect of D1R activation on osteogenic differentiation in Dex-induced MC3T3-E1 cells via the ERK1/2 signaling pathway. In vivo, micro-CT and hematoxylin and eosin (H&E), toluidine blue and immunohistochemical staining were used to determine the effect of D1R activation on Dex-induced bone loss. RESULTS: We demonstrated that the trend in D1R but not D2-5R was consistent with that of osteogenic markers in the presence of Dex. We also demonstrated that the activation of D1R promoted Dex-induced osteogenic differentiation by activating the ERK1/2 pathway in vitro. We further demonstrated that a D1R agonist could reduce Dex-induced bone loss, while pretreatment with a D1R inhibitor blocked the effect of a D1R agonist in vivo. CONCLUSIONS: Activation of D1R promotes osteogenic differentiation and reduces Dex-induced bone loss by activating the ERK1/2 pathway. Hence, D1R could serve as a potential therapeutic target for glucocorticoid-induced osteoporosis.

Abstract Osteolysis around the prosthesis and subsequent aseptic loosening are the main causes of prosthesis failure. Inflammation due to wear particles and osteoclast activation are the key factors in osteolysis and are also potential targets for the treatment of osteolysis. However, it is not clear whether puerarin can inhibit chronic inflammation and alleviate osteolysis. In this study, we investigated the effect of puerarin on Ti particle‐induced inflammatory osteolysis in vivo in rat femoral models and in vitro in receptor activator of nuclear factor kappa‐B ligand (RANKL)‐induced osteoclast activation models. Our in vivo results showed that puerarin significantly inhibited Ti particle‐induced osteolysis and the expression of matrix metallopeptidase 9 (MMP‐9), nuclear factor of activated T cells 1 (NFATc1), tumour necrosis factor (TNF)‐α and interleukin (IL)‐6. In vitro, puerarin prevented RANKL‐induced osteoclast differentiation, bone resorption and F‐actin ring formation in a concentration‐dependent manner. Furthermore, puerarin decreased the phosphorylation of p65 and prevented p65 moving from the cytoplasm to the nucleus. Puerarin also reduced the expression of osteoclast‐specific factors and inhibited the inflammatory response. In conclusion, our study proves that puerarin can block the NF‐κB signalling pathway to inhibit osteoclast activation and inflammatory processes, which provides a new direction for the treatment of osteolysis‐related diseases.