脂质信号分子15d-PGJ2调控牙周炎性微环境下NFATc1介导的破骨细胞分化机制

批准号:
81300881
项目类别:
青年科学基金项目
资助金额:
23.0 万元
负责人:
吴燕岷
依托单位:
学科分类:
H1504.牙周及口腔黏膜疾病
结题年份:
2016
批准年份:
2013
项目状态:
已结题
项目参与者:
陈莉丽、张迪亚、陈晓涛、徐沈杰、黄玫、魏芬
国基评审专家1V1指导 中标率高出同行96.8%
结合最新热点,提供专业选题建议
深度指导申报书撰写,确保创新可行
指导项目中标800+,快速提高中标率
微信扫码咨询
中文摘要
15d-PGJ2是新近发现的具有潜在抗炎作用的脂质信号分子,但对15d-PGJ2调控牙周炎症环境下破骨细胞活动及分子机制尚不明了。项目组在前期研究制备的15d-PGJ2纳米粒、破骨细胞骨吸收及大鼠牙槽骨炎性吸收模型基础上,采用ELISA、TRAP染色和激光共聚焦阐明15d-PGJ2对Pg及RANKL诱导巨噬细胞向破骨细胞分化的影响;用western blot、EMSA、HPLC和质谱分析、生物素标记15d-PGJ2、免疫沉淀和RNA干扰探讨15d-PGJ2调控破骨细胞分化关键分子NFATc1转录活性的分子机制;明确15d-PGJ2纳米粒在体内对牙槽骨吸收量、破骨细胞活动及分化关键调控分子的影响。研究结果将初步揭示15d-PGJ2在牙周炎性微环境下对牙槽骨炎性吸收、破骨细胞分化的影响及调控NFATc1的机制,为将15d-PGJ2作为宿主调节药物用于牙周炎性骨吸收治疗提供科学依据。
英文摘要
15d-PGJ2 is a lipid signaling molecule discovered recently for its anti-inflammation potentials. But the regulation mechanisms and related molecules for 15d-PGJ2 on the activity of osteoclast in an inflammatory periodontal environment need to be investigated. Our group has constructed 15d-PGJ2 loaded nano-capsules with PLGA in previous study, which has been demonstrated to be able to maintain a stale release in in vitro study. We have also established osteoclast bone resorption model as well as rat alveolar bone resorption model. In this study, we plan to use ELISA, TRAP staining and laser confocal microscopy to interpret the effect of 15d-PGJ2 on RANKL induced macrophage to differentiate into osteocalst with co-infection of Pg. With western blot, EMSA, HPLC and mass sepectrum analysis, construction of biotinylated 15d-PGJ2, immuno-precipitation and RNA interference, the molecular mechanism of 15d-PGJ2 on the trancription activity of the key regulator in osteoclast differentiation NFATc1 will be studied. The in vivo effect of 15d-PGJ2 loaded nano-capsules on the level of alveolar bone resorption induced by combination of ligation and infection of Porphyromonas gingivalis, osteoclast activity and the related regulators will also be clarified. The obtained results will reveal the mechanism of 15d-PGJ2's influence on the differentiation of osteoclasts and its regulation of NFATc1 during inflammatory alveolar bone resorption, which will provide scientific evidence for the application of 15d-PGJ2 as a host modulation drug in periodontitis induced alveolar bone resorption.
15d-PGJ2是新近发现的具有潜在抗炎作用的脂质信号分子,但对15d-PGJ2调控牙周炎症环境下破骨细胞活动及分子机制尚不明了。课题组用溶剂扩散法制备载15d-PGJ2及其同系物△12-PGJ2的PLGA纳米粒,建立破骨细胞分化及大鼠牙槽骨吸收模型。采用TRAP染色、实时定量PCR、western blot、EMSA、免疫组化和Masson染色等方法观察了15d-PGJ2对Pg及RANKL诱导巨噬细胞向破骨细胞分化的影响及两种PGJ2纳米粒对骨缺损区的抗炎促成骨作用,结果发现15d-PGJ2可干扰转录因子NFATc1与DNA的结合能力而影响牙周炎性微环境下破骨细胞分化成熟;15d-PGJ2可影响大鼠牙槽骨炎性吸收模型的破骨活动;15d-PGJ2和△12-PGJ2纳米粒可显著抑制骨缺损区的炎性因子表达和转录,促进成骨相关因子表达而发挥促进牙槽骨再生重建的作用。研究结果初步揭示15d-PGJ2在牙周炎性微环境下抑制牙槽骨炎性吸收、破骨细胞分化的影响机制,为将15d-PGJ2及△12-PGJ2作为宿主调节药物用于牙周炎性骨吸收治疗提供科学依据。
期刊论文列表
专著列表
科研奖励列表
会议论文列表
专利列表
DOI:--
发表时间:2015
期刊:中华口腔医学杂志
影响因子:--
作者:孙伟莲;丁佩惠;陈晓涛;吴燕岷
通讯作者:吴燕岷
Possible socioeconomic and oral hygiene behavioural risk factors for self-reported periodontal diseases in women of childbearing age in a Chinese population
中国育龄妇女自报牙周病的可能社会经济和口腔卫生行为危险因素
DOI:--
发表时间:2014
期刊:Oral Health and Preventive Dentistry
影响因子:1.6
作者:刘佳;雷利红;章洁;曹筝
通讯作者:曹筝
DOI:--
发表时间:2016
期刊:吉林大学学报(医学版)
影响因子:--
作者:魏芬;吴燕岷;陈莉丽
通讯作者:陈莉丽
Effect of 15?Deoxy??12,14?prostaglandin J2 Nanocapsules on Inflammation and Bone Regeneration in a Rat Bone Defect Model
15、脱氧、12,14、前列腺素J2纳米胶囊对大鼠骨缺损模型炎症和骨再生的影响
DOI:--
发表时间:--
期刊:Chinese Medical Journal
影响因子:6.1
作者:丁佩慧;谭静怡;陈晓涛;吴燕岷
通讯作者:吴燕岷
IL-17A promotes differentiation and calcification of murine preosteoblastic MC3T3-E1 cells in an AKT2-dependent manner
IL-17A 以 AKT2 依赖性方式促进小鼠前成骨细胞 MC3T3-E1 细胞的分化和钙化
DOI:--
发表时间:--
期刊:Molecular Medicine Reports
影响因子:3.4
作者:陈晓涛;丁佩慧;吴燕岷;陈莉丽
通讯作者:陈莉丽
国内基金
海外基金
