目的:研究双膦酸盐相关颌骨坏死(bisphosphonate-related osteonecrosis of the jaw,BRONJ)病损中信号素4D(semaphorin 4D,Sema4D)的表达变化,探索其在BRONJ发生过程中可能的作用。方法:采用唑来膦酸腹腔注射辅助拔牙构建BRONJ样大鼠模...目的:研究双膦酸盐相关颌骨坏死(bisphosphonate-related osteonecrosis of the jaw,BRONJ)病损中信号素4D(semaphorin 4D,Sema4D)的表达变化,探索其在BRONJ发生过程中可能的作用。方法:采用唑来膦酸腹腔注射辅助拔牙构建BRONJ样大鼠模型,提取上颌骨标本行影像学及组织学检查,体外获取大鼠骨髓单核细胞(bone marrow mononuclear cells,BMMs)及骨髓间充质干细胞(bone marrow mesenchymal stem cells,BMSCs)进行共培养,BMMs破骨向诱导后行细胞Trap染色及计数。在双膦酸盐(bisphosphonates,BPs)环境下,通过破骨定向诱导RAW264.7细胞,检测Sema4D表达差异。体外成骨向定向诱导MC3T3-E1细胞及BMSCs,BPs、Sema4D及Sema4D一抗干预后,检测细胞成骨、破骨相关基因ALP、Runx2和RANKL等的表达差异。采用GraphPad prism 8.0软件对数据进行统计学分析。结果:成功构建BRONJ样大鼠模型。拔牙后2周,实验组拔牙创愈合显著受限,颌骨暴露。H-E染色显示,实验组拔牙窝内新骨再生显著受限,可见死骨形成,拔牙窝软组织愈合受限。Trap染色显示,实验组拔牙窝附近破骨细胞数量显著少于对照组。显微CT扫描显示,实验组拔牙窝内骨密度及骨体积分数显著低于对照组。免疫组织化学染色结果显示,相比于对照组,实验组颌骨内Sema4D表达显著上升。体外研究显示,实验组BMMs破骨细胞向诱导能力显著低于对照组,BMSCs对破骨细胞诱导能力显著降低。破骨向诱导实验发现,BPs有效抑制破骨细胞形成,显著降低Sema4D表达。成骨向诱导实验发现,Sema4D显著降低成骨细胞Runx2、RANKL基因表达;加入Sema4D一抗后,ALP表达显著降低、RANKL表达显著上调。结论:BPs上调组织内Sema4D表达,干扰正常骨愈合时序,导致破骨-成骨偶联紊乱,抑制破骨细胞成熟,进而抑制成骨细胞分化和相关成骨因子表达,介导BRONJ发生。展开更多
A new lanthanide metal-organic framework (MOF)[Eu(BTB)(phen)(DMF)]·DMF (1,DMF=N,N-dimethylformamide) was synthesized using H_(3)BTB (1,3,5-tri(4-carboxyphenyl)benzene) and phen(1,10-phenanthroline) under solvothe...A new lanthanide metal-organic framework (MOF)[Eu(BTB)(phen)(DMF)]·DMF (1,DMF=N,N-dimethylformamide) was synthesized using H_(3)BTB (1,3,5-tri(4-carboxyphenyl)benzene) and phen(1,10-phenanthroline) under solvothermal conditions.The structure of the prepared MOF was characterized by single-crystal X-ray diffraction analyses,elemental analysis,fluorescence spectrum,FT-IR spectroscopy,powder X-ray diffraction and thermogravimetric analyses.The structure of 1 can be viewed as a 3-D supramolecular network,which is formed by the stacking of 2D layers throughπ-πinteraction.The luminescence explorations revealed that 1 possesses favorable selectivity and sensitivity for testing Fe^(3+).Additionally,color tuning was achieved by varying Eu^(3+):Tb^(3+)ratios in the reaction mixtures.展开更多
基金supported by the High-level Teachers in Beijing Municipal Universities in the Period of 13th Five-year Plan (CIT&TCD201904044)URT program of Beijing Institute of Petrochemical Technology (2020J00009)。
文摘A new lanthanide metal-organic framework (MOF)[Eu(BTB)(phen)(DMF)]·DMF (1,DMF=N,N-dimethylformamide) was synthesized using H_(3)BTB (1,3,5-tri(4-carboxyphenyl)benzene) and phen(1,10-phenanthroline) under solvothermal conditions.The structure of the prepared MOF was characterized by single-crystal X-ray diffraction analyses,elemental analysis,fluorescence spectrum,FT-IR spectroscopy,powder X-ray diffraction and thermogravimetric analyses.The structure of 1 can be viewed as a 3-D supramolecular network,which is formed by the stacking of 2D layers throughπ-πinteraction.The luminescence explorations revealed that 1 possesses favorable selectivity and sensitivity for testing Fe^(3+).Additionally,color tuning was achieved by varying Eu^(3+):Tb^(3+)ratios in the reaction mixtures.
