眼眶骨壁菲薄，毗邻副鼻窦空腔，局部血供差，创伤缺损后易造成患者视功能障碍与面部畸形。前期研究表明骨向诱导分化可增强骨髓基质干细胞（BMSC）修复眼眶骨缺损的能力，课题组发现脱甲基化酶Jarid1a可通过甲基化修饰组蛋白显著增强BMSC的成骨分化和骨修复能力。本项目将系统性研究组蛋白甲基化对BMSC成骨分化的调控作用机制和眼眶骨缺损的修复潜能。研究包括：①脱甲基酶Jarid1a基因修饰对BMSC成骨分化的作用；②组蛋白甲基化修饰对成骨基因表达的调控机制；③将组蛋白甲基化修饰BMSC复合磷酸三钙支架材料移植到体内，检测其原位促成骨作用，并用于犬眼眶内侧壁骨缺损模型的修复重建中，探讨其促眼眶骨再生作用。从基因-蛋白-小动物-大动物4个层次，多角度探索组蛋白甲基化在眼眶骨缺损修复中的作用和相关机制，有望为临床上眼眶骨缺损的修复重建提供新方法。

The orbital walls are thin, and adjacent to paranasal sinuses with poor blood supply, where the defects are difficult to repair and may lead to visual dysfunction and facial deformities. Previous studies showed that osteogenic induction of bone marrow mesenchymal stem cell (BMSC) can heighten an effect on orbital bone defects repairing. Histone methylation in nucleosome structure can significantly enhance osteogenic differentiation and bone repair potential of BMSC, The H3K4 demethylase, Jumonji AT-rich interactive domain 1A (Jarid1a) is an important protein by regulating histone methylation level. This proposed study is to systematically investigate the function and regulatory mechanism of histone methylation in osteogenic differentiation of BMSC, and repair the canine medial orbital bone defects using histone methylated BMSC and β- tricalcium phosphate (β-TCP) scaffold. Our approach is to investigate that: ① The effect of gene modification by demethylase Jarid1a on osteogenic differentiation of BMSC; ② The regulatory mechanism of osteogenic gene expression by histone methylation; ③ Detecting in situ osteogenesis of the histone methylated BMSC composited with porous β-TCP scaffold by implantation in vivo, repairing the canine orbital bone defects and investigating the potentials of histone methylated BMSC in orbital bone regeneration. This study will systematically explore the function and mechanisms of histone methylated BMSC in orbital bone defect repair at the levels of gene, protein as well as small and large animals, and be expected to provide new approach for clinical reconstruction of orbital bone defects.