LncRNA HOTTIP调控整合素信号通路参与DDH关节软骨纤维化的分子机制研究

项目名称： LncRNA HOTTIP调控整合素信号通路参与DDH关节软骨纤维化的分子机制研究

项目编号： No.81501844

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 李天友

作者单位： 山东大学

项目金额： 18万元

中文摘要： 如何防止发育性髋关节发育不良（DDH）向骨性关节炎的演变是迫切需要解决的临床问题。新型LncRNA HOTTIP可能通过整合素信号通路参与骨性关节炎的发生。课题组前期研究发现髋臼软骨骨化异常继而纤维化可能是DDH进展为骨性关节炎的病理基础，该过程具有整合素信号通路的参与，机制尚不明确。我们推测HOTTIP通过调控整合素信号通路参与DDH髋臼软骨纤维化过程。本课题拟：1、明确DDH关节软骨中HOTTIP基因的表达与软骨形态学改变之间的关系；2、采用RNA干扰和基因转染技术揭示HOTTIP的表达变化对软骨细胞增殖、凋亡、胶原表达能力的影响；3、采用全基因组表达谱芯片及RNA免疫共沉淀等技术研究HOTTIP调控整合素信号通路的分子机制。本项目对深入阐明HOTTIP在DDH关节软骨纤维化中作用和分子机制，为寻求促进DDH关节软骨发育的药物治疗靶点、防止骨性关节炎的发生具有重要意义。

中文关键词： 发育性髋关节发育不良；关节软骨纤维化；长链非编码RNA；HOTTIP；整合素

英文摘要： How to prevent Developmental dysplasia of the hip (DDH) from becoming to be osteoarthritis is an clinical problem needing to be resolved urgently. The newly found long non-coding RNA HOTTIP is involved in the occurrence of osteoarthritis by regulating integrin signaling pathway, but the mechanism has not been clarified. Our previous study found that the acetabular cartilage fibrosis may be the pathological basis from DDH to osteoarthritis, and the mechanism is related with integrin β1. We speculate HOTTIP contibutes to acetabular cartilage fibrosis in DDH by regulating integrin signaling pathway. This paper intends to: 1. analyze the correlation between the expression of HOTTIP in acetabular cartilage and morphological changes of the cartilage in DDH; 2. clarify the influence of HOTTIP on proliferation, apoptosis and expression of collagen of the chondrocyte by reducing or increasing HOTTIP expression by RNA interference and gene transfection technique in vitro; 3. study the impact of HOTTIP on integrin β1 and downstream molecules by using whole-genome expression microarray, and investigate its molecular mechanisms regulating the integrin β1 by RNA immunoprecipitation, et al. This study is important for elucidating the function of HOTTIP and underlying mechanism in articular cartilage fibrosis in DDH，and for seeking the drug therapy targets to promote the development of the articular cartilage in DDH, and for preventing DDH from becoming to be osteoarthritis.

英文关键词： developmental dysplasia of the hip;articular cartilage fibrosis;LncRNA;HOTTIP;integrin