长链非编码RNA PVT1调控TGF-β1信号通路在糖尿病性骨关节炎中的作用及其机制研究

研究表明糖尿病是骨关节炎的独立危险因素，我国是糖尿病第一大国，糖尿病性骨关节炎严重威胁中老年人的健康与生活质量，而长链非编码RNA可能参与调控该疾病的发生发展。我们的前期工作表明长链非编码RNA PVT1在糖尿病性骨关节炎软骨组织中高表达，其可促进炎症反应和软骨细胞凋亡，并可抑制Ⅱ型胶原分泌、破坏细胞外基质；进一步研究发现其与TGF-β1特异性结合，鉴于TGF-β1信号通路是骨关节炎发病最重要的细胞机制之一，据此我们推测PVT1可能通过调控TGF-β1信号通路促进糖尿病性骨关节炎的发生。本项目拟通过体内外实验，探讨PVT1对软骨细胞增殖、凋亡及细胞外基质分泌的影响；同时采用RNA pulldown，RIP及FISH等技术，阐明PVT1通过靶向调控TGF-β1信号通路促进糖尿病性骨关节炎发生的作用机制。研究结果将丰富糖尿病性骨关节炎的病因学研究，并为糖尿病性骨关节炎的治疗提供新的思路和靶点。

It has been proved that diabetes is an independent risk factor for osteoarthritis. And diabetic osteoarthritis has been individualised based on recent research. Meantime China is now among the countries with the highest diabetes prevalence. So we need to pay more attention to diabetic osteoarthritis. Diabetic osteoarthritis is responsible for pain, functional decline, and affects health and quality of life of the older population. Recent evidence suggests that lncRNA may play a major role in regulating multiple diseases. Our study found that the highly expressed PVT1 promoted the development and progression of diabetic osteoarthritis through mechanisms involving inflammation, chondrocyte apoptosis, inhibition of type Ⅱ collagen secretion and destruction of the extracellular matrix. We also found that PVT1 bound to TGF-β1. And it is generally known that TGF-β1 signal pathway is crucial for the pathogenesis of OA. As a result, we infer that TGF-β1 signal pathway mediated by PVT1 induce diabetic osteoarthritis. To demonstrate this, we will mediate the PVT1 expression level in vitro and vivo study respectively. Then we will evaluate the function of PVT1 on the biological characteristics. To understand the potential mechanisms, RNA pulldown, RIP and FISH are used to validate the interaction protein and potential target. Overall, there has an urgent need to thoroughly understand the function of PVT1 on the biological characteristics. This will enhance the understanding of disease mechanisms responsible for diabetic osteoarthritis and lead to novel and improved therapeutic strategies and targets for this chronic condition.