microRNA-1在骨关节炎关节软骨肥大中的调控机制和靶向治疗的研究

The pathogenesis of Osteoarthritis (OA) remains unknown, and we have not efficient methods that prevent the degeneration of articular cartilage associated with osteoarthritis. Recent evidence suggests that Indian hedgehog (Ihh), a bioactive protein, may promote OA development by driving chondrocyte hypertrophy. Cartilage degradation in OA is mediated by microRNAs. Our previous study found that there are two receptors between microRNA-1(miR-1) and Ihh 3’UTR. When miR-1 is upregulated, the Ihh gene and downstream protein expression can be inhibited. There are no researchs focus on miR-1 inhibits OA development indirectly by regulating Ihh signaling. To explore the role of miR-1 in OA, we used a miR-1 overexpression mice and LNP-miR-1. To test this hypothesis, in vivo by fluorescence molecular tomography (FMT) and several other conventional methods will be used. The clinical implication of our study is that targeting miR-1 by regulating Ihh signaling may be a viable strategy to prevent or treat OA.

骨关节炎（OA）病因及发病机制不明，目前尚无有效阻止其进程的方法。最近研究表明，Indian hedgehog （Ihh）通过诱导软骨细胞肥大样改变，进而促进软骨退变参与OA的发生发展进程。microRNAs在OA病理进程中起调控作用。我们前期的体内体外研究发现：microRNA-1（miR-1）与Ihh 3’UTR有两个结合位点，且miR-1高表达可抑制Ihh基因及蛋白的表达。目前国内外尚无关于miR-1通过Ihh调控软骨细胞肥大在OA病理进程中的作用及机制研究的报道。本课题组拟在体内体外研究的基础上，应用质粒转染、结合条件性过表达miR-1基因小鼠和LNP-miR-1软骨递送系统，运用活体荧光分子断层扫描及其他常规手段，探求miR-1通过Ihh基因调控软骨细胞肥大，延缓和阻滞骨关节炎软骨细胞肥大样改变进程中的作用与机制，为OA的靶向治疗提供可行方案。

骨关节炎（OA）病因及发病机制不明，目前尚无有效阻止其进程的方法。最近研究表明，Indian hedgehog （Ihh）通过诱导软骨细胞肥大样改变，进而促进软骨退变参与OA的发生发展进程。本研究采用体外、体内实验对其机制进行探索，发现microRNA-1（miR-1）与Ihh 3’UTR有两个结合位点，且miR-1高表达可抑制Ihh通路上，IHH及下游基因及蛋白的表达。通过条件性过表达miR-1基因小鼠结合骨关节炎模型，与大鼠骨关节炎体外转染过表达miR-1模型，运用活体荧光分子断层扫描及其他常规手段，证实miR-1通过Ihh基因调控软骨细胞肥大，延缓和阻滞骨关节炎软骨细胞肥大样改变进程中的作用与机制，为OA的靶向治疗提供可行方案。