目的探讨续断皂苷VI调控Wnt/β-Catenin通路对骨质疏松的影响并分析其作用机制。方法构建SPF级Wistar大鼠骨质疏松症模型与健康大鼠共同饲养形成对照组,将50只雌性大鼠随机分为4组。依次设置为:续断皂苷VI治疗组,模型对照组,假手术组,...目的探讨续断皂苷VI调控Wnt/β-Catenin通路对骨质疏松的影响并分析其作用机制。方法构建SPF级Wistar大鼠骨质疏松症模型与健康大鼠共同饲养形成对照组,将50只雌性大鼠随机分为4组。依次设置为:续断皂苷VI治疗组,模型对照组,假手术组,空白对照组。使用不同双侧卵巢摘除手术法处理实验组大鼠。除空白对照组外,模型对照组与假手术组以及续断皂苷VI处理组的大鼠均制成骨质疏松症大鼠模型,将续断皂苷VI组的大鼠连续给药12周。使用X线骨密度仪骨密度(BMD,bone mineral density)测定法检测各组大鼠BMD,观察给药前后大鼠BMD变化情况;使用生物力学测定仪测定各组大鼠后肢股骨的最大载荷差异;使用RT-PCR实验和Western Blotting实验以检测不同组Wnt3a、β-catenin、LRP5、Runx2、SOST和Osx转录组与蛋白组表达各自发生的差异。结果续断皂苷VI治疗12周可显著提高骨质疏松症大鼠模型股骨的BMD,并提高椎体在最大负荷和弹性模量下的生物力学能力,降低了骨质疏松症在骨组织中造成的致病性。对于组织形态学方面的考察发现,续断皂苷VI治疗组在治疗持续12周后,小梁排列整齐,小梁稍变薄,股骨没有明显的轻微骨折。在进行续断皂苷VI治疗处理的情况下,经典Wnt/β-catenin信号通路中涉及的LRP5、β-catenin、Runx2和Osx的表达显著上调,而在该通路中SOST的表达下调(P<0.05)。结论续断皂苷VI可显著提高骨质疏松模型大鼠的骨密度,其保护机制与激活Wnt/β-catenin信号通路,上调骨质疏松大鼠骨中β-catenin、LRP5的mRNA表达有相关。展开更多
Heterosis represents one of the most revolutionary advancements in crop improvement.In the genetic dissection of heterosis,NCIII design is one of the most powerful and widely used mating schemes.However,the methodolog...Heterosis represents one of the most revolutionary advancements in crop improvement.In the genetic dissection of heterosis,NCIII design is one of the most powerful and widely used mating schemes.However,the methodologies for quantitative trait loci (QTL) detection in the design were mostly based on composite interval mapping.Therefore,in this study,our purpose was to develop a statistical method for mapping epistatic QTL associated with heterosis in the RIL-based NCIII design.First,we derivated the expectations of two classical linear transformations,Z 1 and Z 2,while a quantitative trait was controlled by two QTL with digenic epistasis and arbitrary linkage under the F ∞ and F 2 metric models.Then,we constructed an epistatic genetic model that includes all markers on the whole genome simultaneously,and estimated all the parameters in the model by the empirical Bayes approach.Finally,a series of Monte Carlo simulation experiments was carried out to confirm the proposed approach.The results show that:(1) all the augmented genetic parameters for main-effect QTL could be rightly identified with satisfactory statistical power and precision;(2) the statistical powers in the detection of augmented epistatic effects were substantively affected by the signs of pure epistatic effects;(3) it is more difficult to detect epistatic QTL than to detect main-effect QTL;(4) statistical power is higher in the RIL-based NCIII design than in the F 2-based NCIII design,especially in the detection of the augmented epistatic effect that consists of two pure epistatic effects in opposite directions.展开更多
文摘目的探讨续断皂苷VI调控Wnt/β-Catenin通路对骨质疏松的影响并分析其作用机制。方法构建SPF级Wistar大鼠骨质疏松症模型与健康大鼠共同饲养形成对照组,将50只雌性大鼠随机分为4组。依次设置为:续断皂苷VI治疗组,模型对照组,假手术组,空白对照组。使用不同双侧卵巢摘除手术法处理实验组大鼠。除空白对照组外,模型对照组与假手术组以及续断皂苷VI处理组的大鼠均制成骨质疏松症大鼠模型,将续断皂苷VI组的大鼠连续给药12周。使用X线骨密度仪骨密度(BMD,bone mineral density)测定法检测各组大鼠BMD,观察给药前后大鼠BMD变化情况;使用生物力学测定仪测定各组大鼠后肢股骨的最大载荷差异;使用RT-PCR实验和Western Blotting实验以检测不同组Wnt3a、β-catenin、LRP5、Runx2、SOST和Osx转录组与蛋白组表达各自发生的差异。结果续断皂苷VI治疗12周可显著提高骨质疏松症大鼠模型股骨的BMD,并提高椎体在最大负荷和弹性模量下的生物力学能力,降低了骨质疏松症在骨组织中造成的致病性。对于组织形态学方面的考察发现,续断皂苷VI治疗组在治疗持续12周后,小梁排列整齐,小梁稍变薄,股骨没有明显的轻微骨折。在进行续断皂苷VI治疗处理的情况下,经典Wnt/β-catenin信号通路中涉及的LRP5、β-catenin、Runx2和Osx的表达显著上调,而在该通路中SOST的表达下调(P<0.05)。结论续断皂苷VI可显著提高骨质疏松模型大鼠的骨密度,其保护机制与激活Wnt/β-catenin信号通路,上调骨质疏松大鼠骨中β-catenin、LRP5的mRNA表达有相关。
基金supported by the National Basic Research Program of China(2011CB109306)a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions+1 种基金the National Natural Science Foundation of China(30900842,31000666)the NAU Youth Sci-Tech Innovation Fund(KJ08001)
文摘Heterosis represents one of the most revolutionary advancements in crop improvement.In the genetic dissection of heterosis,NCIII design is one of the most powerful and widely used mating schemes.However,the methodologies for quantitative trait loci (QTL) detection in the design were mostly based on composite interval mapping.Therefore,in this study,our purpose was to develop a statistical method for mapping epistatic QTL associated with heterosis in the RIL-based NCIII design.First,we derivated the expectations of two classical linear transformations,Z 1 and Z 2,while a quantitative trait was controlled by two QTL with digenic epistasis and arbitrary linkage under the F ∞ and F 2 metric models.Then,we constructed an epistatic genetic model that includes all markers on the whole genome simultaneously,and estimated all the parameters in the model by the empirical Bayes approach.Finally,a series of Monte Carlo simulation experiments was carried out to confirm the proposed approach.The results show that:(1) all the augmented genetic parameters for main-effect QTL could be rightly identified with satisfactory statistical power and precision;(2) the statistical powers in the detection of augmented epistatic effects were substantively affected by the signs of pure epistatic effects;(3) it is more difficult to detect epistatic QTL than to detect main-effect QTL;(4) statistical power is higher in the RIL-based NCIII design than in the F 2-based NCIII design,especially in the detection of the augmented epistatic effect that consists of two pure epistatic effects in opposite directions.
