影响骨关节炎发生发展的新机制：缓激肽B2受体基因多态性

Osteoarthritis (OA) is a degenerative joint disease that progressively causes loss of joint function and is a major source of physical disability and impaired quality of life. The etiology of OA is largely unknown, it is now accepted that the genetic factors play a significant role in the molecular pathogenesis of OA. B2-bradykinin receptor (BDKRB2) which is widely present in most tissues including joint tissues, mediates most of the inflammatory actions of bradykinin. Although the role of BDKRB2 in inflammation has been documented, we did not find any reports with regard to the genetic polymorphisms of BDKRB2 gene and inflammation. In the previous study which was pressed in the Journal of Biomedicine and Biotechnology, we firstly reported the role of genetic polymorphisms of BDKRB2 in the onset and progression of OA in the chinese cohort. This finding suggests that the BDKRB2 polymorphisms may be used as a genetic marker for the onset and development of OA, and then be a important clinical screening method in OA patients. To test this hypothesis, we will enlarge the sample content, adopt the technology of molecular biology and gene sequencing. Then, we would evaluate the effect of bradykinin B2 receptor polymorphisms on the susceptibility and severity of osteoarthritis and explore the signal transducing pathway. We will explain the molecular mechanism of the onset and development of OA from a new point of view, and it could be a therapeutic target in the prevention and treatment of OA.

骨关节炎（OA）是一种导致关节功能逐渐丧失的退行性关节疾病，令患者致残并影响其生活质量。骨关节炎的病因尚不明确，遗传因素近来被认为是骨关节炎的重要发病机制之一。 缓激肽B2受体（BDKRB2）广泛存在于包括关节组织在内的各种组织，介导了大多数缓激肽引起的炎症反应。尽管缓激肽B2受体在炎症中的作用已被阐明，但国内外尚无关于缓激肽B2受体基因多态性与炎症关系的研究。申请人在JBB杂志发表的前期研究报告中，首次发现了在华人群体中缓激肽B2受体基因多态性与骨关节炎的易感性和严重性有关，提示缓激肽B2受体基因多态性可能作为骨关节炎发生和发展的基因标记，成为重要的临床筛查指标。 为验证这一假说，我们扩大样本含量，采用分子生物学、基因测序等技术，观察BDKRB2对骨关节炎发生和发展的影响及其信号传导通路。本课题将从新的角度阐明骨关节炎发生发展的分子机制，并为骨关节炎的治疗提供新思路和新靶点。

骨关节炎（OA）是一种导致关节功能逐渐丧失的退行性关节疾病，令患者致残并影响其生活质量。骨关节炎的病因尚不明确，遗传因素近来被认为是骨关节炎的重要发病机制之一。缓激肽B2受体（BDKRB2）广泛存在于包括关节组织在内的各种组织，介导了大多数缓激肽引起的炎症反应。尽管缓激肽B2受体在炎症中的作用已被阐明，但国内外尚无关于缓激肽B2受体基因多态性与炎症关系的研究。申请人在JBB杂志发表的前期研究报告中，首次发现了在华人群体中缓激肽B2受体基因多态性与骨关节炎的易感性和严重性有关，提示缓激肽B2受体基因多态性可能作为骨关节炎发生和发展的基因标记，成为重要的临床筛查指标。为验证这一假说，我们扩大样本含量，采用分子生物学、基因测序等技术，观察BDKRB2对骨关节炎发生和发展的影响及其信号传导通路。本课题将从新的角度阐明骨关节炎发生发展的分子机制，并为骨关节炎的治疗提供新思路和新靶点。