掺锶介孔生物活性玻璃负载双膦酸盐改善去卵巢小鼠骨流失  

Strontium-containing mesoporous bioactive glass nanoparticles loaded with bisphosphonates ameliorate bone loss in ovariectomized mice

作　　者：周志 陈致介 霍市城 李展春[1] Zhou Zhi;Chen Zhijie;Huo Shicheng;Li Zhanchun(Department of Orthopedics,Renji Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200127,China;Department of Minimally Invasive Spine,Changzheng Hospital,Chinese People’s Liberation Army Navy Military Medical University,Shanghai 200003,China)

机构地区：[1]上海交通大学医学院附属仁济医院骨科,上海市200127 [2]中国人民解放军海军军医大学附属长征医院脊柱微创科,上海市200003

出　　处：《中国组织工程研究》2024年第17期2653-2658,共6页Chinese Journal of Tissue Engineering Research

基　　金：上海市科委计划项目(21140904600),项目负责人:李展春。

摘　　要：背景:双膦酸盐通过抑制破骨细胞活性延缓骨质疏松进展,然而双膦酸盐严重的并发症如下颌骨坏死、非典型性股骨骨折等严重限制了其临床应用,需要寻求有效的替代疗法改善现有的临床困局。目的:制备掺锶介孔生物活性玻璃负载双膦酸盐(BPS@Sr-MBG),分析其抗骨质疏松活性。方法:采用溶胶-凝胶法制备掺锶介孔生物活性玻璃,然后加入阿仑膦酸盐饱和溶液中制备BPS@Sr-MBG。①细胞实验:将小鼠骨髓巨噬细胞接种于96孔板内,加入含巨噬细胞集落刺激因子、核因子κB受体活化子配体的ɑ-MEM完全培养基进行破骨细胞诱导分化实验,同时分3组培养,空白组加入PBS,对照组加入双膦酸盐,实验组加入BPS@Sr-MBG。培养5 d后,F-肌动蛋白环染色观察破骨细胞分化情况。②动物实验:将24只雌性C57/BL小鼠随机分为4组,每组6只。除假手术组外,切除去卵巢组、BPS组、BPS@Sr-MBG组小鼠双侧卵巢构建骨质疏松模型,造模1周后,BPS组、BPS@Sr-MBG组小鼠分别腹腔注射双膦酸盐溶液、BPS@Sr-MBG溶液,假手术组、去卵巢组小鼠腹腔注射PBS,1次/周。连续注射8周后,取小鼠股骨进行Micro-CT扫描及苏木精-伊红染色分析。结果与结论:①细胞实验:F-肌动蛋白环染色显示,与空白组比较,对照组破骨细胞面积占比与破骨细胞数量均减少(P<0.01);与对照组比较,实验组破骨细胞面积占比与破骨细胞数量均减少(P<0.01)。②动物实验:股骨Micro-CT扫描结果显示,与假手术组比较,去卵巢组小鼠骨密度、骨小梁骨体积分数、骨小梁厚度、骨小梁数目均降低(P<0.05,P<0.01),骨小梁间距、结构模型指数升高(P<0.01);与去卵巢组比较,BPS组、BPS@Sr-MBG组小鼠上述骨参数均得到明显改善(P<0.01),其中以BPS@Sr-MBG组各指标改善更明显。股骨苏木精-伊红染色进一步证实了Micro-CT扫描结果。③结果表明:BPS@Sr-MBG可通过抗破骨效应与促骨形成发挥抗骨�BACKGROUND:Inhibition of osteoclast activity by bisphosphonates slows the progression of osteoporosis.However,serious complications of bisphosphonates,such as osteonecrosis of the jaw and atypical femur fracture,limit the clinical application of bisphosphonates.Effective alternative therapies need to be sought to improve existing clinical dilemmas.OBJECTIVE:To prepare strontium-containing mesoporous bioactive glass nanoparticles loaded with bisphosphonates(BPS@Sr-MBG)and analyze its activity against bone loss.METHODS:Strontium-containing mesoporous bioactive glass nanoparticles(Sr-MBG)were prepared by sol-gel method and added to alendronate saturated solution for the preparation of BPS@Sr-MBG.(1)Cell experiment:Mouse bone marrow macrophages were inoculated in 96-well plates and supplemented with ɑ-MEM complete culture medium containing macrophage colony stimulating factor and activator-ligand of nuclear factorκB receptor for osteoclast induced differentiation experiment.Meanwhile,they were cultured in three groups.The blank group was added with PBS.The control group was added with bisphosphonate,and the experimental group was added with [e-mail] 5 days of culture,the differentiation of osteoclasts was observed by F-actin ring staining.(2)Animal experiments:Twenty-four female C57/BL mice were randomly divided into four groups with six mice in each group.Except sham operation group,ovariectomy group,BPS group and BPS@Sr-MBG group were used to construct osteoporosis model.One week after model establishment,mice in BPS group and BPS@Sr-MBG group were intraperitoneally injected with bisphosphonate solution and BPS@Sr-MBG solution,respectively.Mice in the sham operation group and ovariectomy group were intraperitoneally injected with PBS once a week.After 8 weeks of continuous injection,mouse femurs were taken for Micro-CT scanning and hematoxylin-eosin staining.RESULTS AND CONCLUSION:(1)Cell experiment:F-actin ring-formation staining demonstrated that compared with blank group,the area proportion and number

关 键 词：骨质疏松 生物活性玻璃 锶离子 双膦酸盐 骨流失 骨髓巨噬细胞 

分 类 号：R453.9[医药卫生—治疗学] R318[医药卫生—临床医学] TQ132.33[化学工程—无机化工]