BMK1信号通路在维持骨髓间充质干细胞成脂分化和成骨分化平衡中的表观遗传学研究

骨质疏松患者骨组织内存在异常数量的脂肪细胞，其发生机制尚不清楚。我们前期研究提示抑制正常小鼠体内BMK1信号通路后，骨量出现减少，微观研究发现脂肪细胞异常增多而成骨细胞减少，提示BMK1信号通路对于维持骨髓间充质干细胞（BMSCs）成脂分化和成骨分化的平衡至关重要。过氧化物酶体增殖物激活受体（PPARγ）、CCAAT/ 增 强 子 结 合 蛋 白-α（C/EBPα）和Runt相关转录因子2（RUNX2）与BMSCs的成脂分化和成骨分化调控具有密切的关系，我们的前期研究结果提示上述关键因子的DNA甲基化水平与抑制BMK1信号通路相关的小鼠骨量减少有关。本研究拟从整体水平、细胞水平和分子水平三个层次来进行研究，通过形态学、细胞学、分子生物学和表观遗传学的研究来阐明BMK1信号通路调控间充质干细胞成脂分化和成骨分化平衡的表观遗传学分子机制，丰富骨质疏松形成机制，为临床相关治疗提供新的理论依据。

More adipocytes are detected in clinical osteoporotic patients, but the mechanisms underlying it remain largely unknown. Our previous studies have shown that the inactivation of BMK1 signaling pathways resulted in low bone mass, more adipocytes, and less osteoblasts in mice. We postulated that activated BMK1 signaling pathways can maintain the homeostasis of osteogenesis and adipogenesis in bone marrow stromal cells (BMSCs). Peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), and Runt-related transcription factor 2 (RUNX2) may regulate adipogenesis and osteogenesis of BMSCs, and DNA methylation is a very pivotal differentiation mechanisms. BMK1 AND DNA methylation might be involved in the aforementioned differentiation mechanisms. To test this hypothesis, we will conduct a morphological, cytological, molecular, and epigenetic experiments at molecular level, cellular level, and systematic biological level. In this study, we examined the significant relationships between BMK1 signaling pathways and epigenetic landscape in the processes of osteogenesis and adipogenesis of BMSCs. This study will enrich the modulation theory of osteoporosis and may provide theoretic support and new potential target for treatment of osteoporosis.