随着我国人口的老龄化，骨质疏松的发病率将迅速上升，给国家经济和社会带来沉重的负担。深入研究骨质疏松发病机制，寻找防治骨质疏松的新策略，具有重要的意义。肌肉细胞在骨质疏松发病中具有重要作用。申请者前期发现，骨质疏松患者肌肉细胞、血清和血清外泌体中组蛋白H3K79甲基转移酶DOT1L低表达。DOT1L通过MPTP打开影响肌肉细胞分泌Irisin，调节成骨细胞分化、破骨细胞分化和蚀骨能力，但具体分子机制需要进一步阐明。因此，本项目将进行如下研究：1.明确DOT1L表观调控CypD基因转录的具体分子机制；2.DOT1L介导的MPTP的打开是否通过ROS/Sirt1/PGC1-α通路，对FNDC5表达和Irisin分泌进行调节；3.探索肌肉细胞DOT1L-MPTP-Irisin通路中骨质疏松诊治的新靶点。通过以上研究，希望为骨质疏松的诊断和防治提供新的策略和理论支持。

As China's population ages, the incidence of osteoporosis will rise rapidly, putting a heavy burden on the national economy and society. It is of great significance to study the pathogenesis of osteoporosis and find new strategies to prevent and treat osteoporosis. Muscle cells play an important role in the pathogenesis of osteoporosis. The applicant of this project found that the expression of histone H3K79 methyltransferase DOT1L was low in muscle cells, serum and serum derived exosome of patients with osteoporosis. DOT1L can affect the secretion of Irisin by muscle cells to regulate osteoblast differentiation, osteoclast differentiation and bone erosion through MPTP opening, but the specific molecular mechanism needs further clarification. Therefore, the project is planned to conduct the following studies: 1. To clarify the specific molecular mechanism by which DOT1L epigenetically regulates the transcription of CypD gene; 2. Does DOT1L-mediated opening of MPTP regulate FNDC5 expression and Irisin secretion through the ROS/Sirt1/PGC1-α pathway? 3. Explore whether there is a new target for the diagnosis and treatment of osteoporosis in the DOT1L-MPTP-Irisin pathway in muscle cells. Through the above research, it is hoped to provide new strategies and theoretical support for the diagnosis and prevention of osteoporosis.