lnc-NR_045553通过miR-17-5p/FGD5介导强直性脊柱炎骨化的机制研究

强直性脊柱炎（AS）是遗传相关性显著的自身免疫性疾病，近1/3患者晚期髋关节骨化强直，严重致残，但其病理性成骨的机制仍不明确。申请人长期从事AS病理成骨机制，前期工作中重点研究异常成骨的髋关节韧带干细胞，通过高通量芯片建立了多个ceRNA调控轴构成的调控网络。我们筛选后发现lnc-NR_045553/miR-17-5p/FGD5的ceRNA调控轴与成骨有关，可能发挥关键作用。FGD5可能通过抑制PI3K/Akt通路影响韧带干细胞成骨。本项目拟利用RNA免疫共沉淀（RIP）技术、CRISPR-Cas9等技术在韧带干细胞、基因敲除小鼠和临床标本中研究上述ceRNA调控轴并明确FGD5调控成骨的机制。本课题的完成将为AS的分子诊断和个体化治疗提供新的思路，并为相关靶点将来的临床转化奠定理论基础。

Ankylosing spondylitis (AS) is an autoimmune disease with significant genetic correlation. Almost one third of patients suffer from hip joint ankylosis at end stage and the pathogenesis is still unclear. The applicant has long been engaged in the pathogenesis of AS pathology. In the previous work, we focused on abnormal osteogenesis of mesenchymal stem cells (MSCs) derived from the ligament and constructed multiple ceRNA axis regulatory networks of hip joint ligament through gene chip and bioinformatics analysis. After screening, we found that the ceRNA regulation axis of lnc-NR_045553/miR-17-5p/FGD5 is associated with osteogenesis, which may play a key role in AS. FGD5 may affect the osteogenesis of ligament MSCs by inhibiting the PI3K/Akt pathway. The aim of this project is to study the ceRNA regulatory axis and clarify the mechanism of FGD5 regulating bone formation by RNA immunoprecipitation (RIP), CRISPR-Cas9 technology and other related technology in ligament MSCs, knockout mice and clinical specimens. This study would provide new ideas for the molecular diagnosis and individualized treatment of AS and lay the theoretical basis for applying related targets into translational medicine.