股骨头坏死发生中非编码RNA调控网络及干预措施的研究

Corticosteroid is the most common Etiological Factor causing osteonecrosis of femoral head in Chinese population, bringing a great burden on the society and family. Cliniclly, we observed that some long- term steroid users live without ONFH, while ONFH occurs at some with short-term usage. Our researches has demonstrated that mir-23a and mir-216a could regulate the development of Steroid-induced femoral head necrosis through different signal pathways. And other non-coding RNA, such as lncRNA and circRNA ,function through interacting with miRNA. The current study aims to screen out the differences in expression of non-coding RNA through chip comparative analysis combined with bioinformatic prediction between ONFH patients with short-term corticosteroids and non-ONFH patients with long-term corticosteroids. Then we plan to overexpress or silence the target non- coding RNA in human bone marrow stem cell and to investigate their effect on BMSC and the potential mechanisms using molecular biology technique, furthermore, we plan to reveal the network of non- coding RNA centered on miRNA, then verify our results in animal models. At last we try to evaluate the possibility of the molecules in the signal pathways as intervention methods in ONFH.

股骨头坏死（ONFH）给社会带来沉重负担，其发病机制尚不清楚，激素是其最常见病因。我们观察到有的患者长期使用激素不发生ONFH，有的患者短期使用激素即发生ONFH。我们的研究证实，mir-23a与mir-216a通过影响不同信号通路，在ONFH的发病中起重要调控作用。各种非编码RNA，如lncRNA及circRNA可通过与miRNA相互作用发挥作用。本研究拟通过芯片对比分析，并用生物信息学方法筛选短期使用激素即发生ONFH患者与长期使用激素未发生ONFH患者间差异性表达的非编码RNA；采用分子生物学技术，在骨髓间质干细胞中模拟其高表达或低表达，研究其对于BMSC功能的影响，并以miRNA为核心，研究非编码RNA调控网络，构建非编码RNA调控激素性股骨头坏死发生发展的网络，并在动物水平进行验证。同时，进一步探究非编码RNA及其通路上分子作为SFHN干预手段的可能性。

股骨头坏死（ONFH）给社会带来沉重负担，其发病机制尚不清楚，激素是其最常见病因。我们观察到有的患者长期使用激素不发生ONFH，有的患者短期使用激素即发生ONFH。我们的研究证实，mir-23a与mir-216a通过影响不同信号通路，在ONFH的发病中起重要调控作用。各种非编码RNA，如lncRNA及circRNA可通过与miRNA相互作用发挥作用。本研究拟通过芯片对比分析，并用生物信息学方法筛选短期使用激素即发生ONFH患者与长期使用激素未发生ONFH患者间差异性表达的非编码RNA；采用分子生物学技术，在骨髓间质干细胞中模拟其高表达或低表达，研究其对于BMSC功能的影响，并以miRNA为核心，研究非编.码RNA调控网络，构建非编码RNA调控激素性股骨头坏死发生发展的网络，并在动物水平进行验证。同时，进一步探究非编码RNA及其通路上分子作为SFHN干预手段的可能性。