SC-514, a selective inhibitor of IKKβ attenuates RANKL-induced osteoclastogenesis and NF-κB activation

The RANKL-induced NF-κB signaling pathway is essential for osteoclastogenesis. This study aims to identify specific inhibitors targeting NF-κB signaling pathway, which might serve as useful small molecule inhibitors for the treatment and alleviation of osteoclast-mediated bone lytic diseases. By screening for compounds that selectively inhibit RANKL-induced NF-κB activation in RAW264.7 cells as monitored by luciferase reporter gene assay, we identified SC-514, a specific inhibitor of IKKβ, as a candidate compound targeting osteoclastogenesis. SC-514 dose-dependently inhibits RANKL-induced osteoclastogenesis with an IC50 of <5 μM. At high concentrations, SC-514 (≥12.5 μM) induced apoptosis and caspase 3 activation in RAW264.7 cells. Moreover, SC-514 specifically suppressed NF-κB activity owing to delayed RANKL-induced degradation of IκBα and inhibition of p65 nuclear translocation. Taken together, our results indicate that SC-514 impairs RANKL-induced osteoclastogenesis and NF-κB activation. Thus, targeting IKKβ by SC-514 presents as a potential treatment for osteoclast-related disorders such as osteoporosis and cancer-induced bone loss.     

异体皮质骨板在严重骨缺损股骨翻修中的应用

21世纪,随着关节外科技术的进步和日臻完善,人工关节假体的临床应用数量不断增加,使用年限不断延长,相关的翻修数量也在逐年上升。2000年,全美共行183000例全髋关节置换,其中翻修手术31000例,占17％左右。比起初次的髋关节置换,全髋翻修面对的患者情况多变复杂,手术难度大,要求的手术技术高,     

The function of SOX2 in breast cancer and relevant signaling pathway

ObjectiveThe purpose of this study was to explore the functional roles of SOX2 in the progression of breast cancer and relevant molecular mechanism.MethodsA total of 108 breast cancer patients were included, and breast cancer cell line MDA-MB-231 was selected for this research. Real time-qualitative polymerase chain reaction (RT-qPCR) was conducted to measure the expression level of SOX2 mRNA. MTT and Transwell assays were used to detected the proliferation, migration and invasion of breast cancer cells, respectively. Luciferase reporter assay was conducted to reveal the relationship of SOX2 with PTEN. Western blot was performed to detect the expressions of Wnt/β-catenin pathway-related proteins.ResultsThe expression of SOX2 mRNA was up-regulated in breast cancer tissues and cells (P < 0.001). SOX2 expression was significantly associated with TNM stage and lymph node metastasis of breast cancer patients (P < 0.05). SOX2 knockdown significantly inhibited the proliferation, migration and invasion of breast cancer cells (P < 0.05). PTEN was a direct target of SOX2. The inhibition of PTEN could significantly suppress the progression of breast cancer cells with SOX2 overexpression. SOX2 knockdown also inhibited the expressions of β-catenin, TCP-4, FZD7, C-myc and MMP-7 proteins. Moreover, PTEN knockdown reversed the results caused by SOX2 overexpression, that is, increased expressions of β-catenin, TCP-4, FZD7, C-myc and MMP-7 proteins (P < 0.05).ConclusionSOX2 promotes the progression of breast cancer through activating Wnt/β-catenin signaling pathway via regulating PTEN.     

不同异体皮质骨板桥接股骨缺损的实验研究

[目的]观察冷冻组、酒精组、新鲜组异体皮质骨板桥接兔股骨缺损处的生物力学、影像学及组织学变化的差异。[方法]将制备好的冷冻、酒精储存和新鲜异体皮质骨板分别植入随机分组的3组大白兔股骨缺损处，植入后4、8、12周取材，从生物力学、影像学及组织学方面分析3种异体皮质骨板在兔体内的生物学变化过程。[结果]术后4周冷冻、酒精、新鲜组弯曲应力及位移相近，8、12周前2组较新鲜组有很大差异。术后12周冷冻、酒精组X线片均见异体皮质骨与宿主骨融合一体，新鲜组则未见融合。术后4周冷冻、酒精组出现成骨细胞，新鲜组未见；术后8周冷冻、酒精组有连续排列的成骨细胞，新鲜组仅见少量不连续的成骨细胞；术后12周冷冻、酒精组见大量连续排列的成骨细胞，新鲜组仅见排列连续的成骨细胞。[结论]冷冻、酒精储存异体皮质骨板和新鲜异体皮质骨板均具有初期生物力学的支撑功能；酒精储存异体骨板和冷冻异体骨板均能达到宿主骨-异体骨融合，而新鲜异体骨板由于免疫排斥反应其宿主骨-异体骨愈合能力较差。