钙磷涂层镁合金通过circ-znf532/miR-370-3p/OSM-gp130轴调控眼眶局部免疫微环境及骨再生的研究

眼眶骨折、炎症和肿瘤等造成眶骨缺损后，由于眶壁菲薄，成骨细胞少，紧邻鼻窦炎症微环境，缺损难以修复。研发眶骨修复材料，关注其对干细胞成骨分化的直接调控及对免疫微环境的管理，有望改善这一现状。我们前期发现镁合金修复眶骨过程中，环状RNA（circ-znf532）介导了骨髓间充质干细胞（BMSC）及巨噬细胞间的协调作用：镁合金浸提液培养后，BMSC高表达circ-znf532，巨噬细胞高表达OSM，且靶基因预测和双荧光素酶实验发现源自BMSC的circ-znf532通过竞争性结合miR-370-3p，显著增强靶基因gp130（OSM受体）的翻译，从而增强BMSC对OSM的反应性，提示镁合金通过circ-znf532/miR-370-3p/OSM-gp130通路介导了BMSC和巨噬细胞的协同促眶骨修复作用。本课题拟探讨circ-znf532促眶骨修复的作用及机制，为解决临床眶骨修复难题提供新思路。

The orbital bone defect caused by orbital fracture, inflammation and tumor is difficult to repair due to the thin bone in the orbital wall and the lack of osteoblasts, which are close to the inflammatory microenvironment of the paranasalsinus.The research and development of orbital bone repair materials, focusing on the direct regulation of stem cell osteogenic differentiation and the management of immune microenvironment, is expected to improve this situation.We previously found that circRNA (circ-znf532) mediated the coordination between bone marrow mesenchymal stem cells (BMSCs) and macrophages in the process of magnesium (Mg) alloy repair of orbital bone: when coculture BMSCs with macrophages in Mg-extract solution, BMSCs highly expressed the circ-znf532, and macrophages highly expressed OSM, and target gene prediction and dual luciferase results showed that the circ-znf532 originated from BMSCs competitively combined miR-370-3p, resulting in significantly enhanced target gene gp130 (OSM receptor) translation, thus increasing the BMSC reactivity to OSM, which promote BMSC osteogenesis.This study intends to explore the role and mechanism of circ-znf532 in promoting orbital bone repair, so as to provide a new idea for solving the clinical orbital bone repair problem.