Hedgehog信号介导的自噬途径在斑马鱼成骨细胞分化与活性中的作用研究

Osteoblast is responsible for bone formation,the disorder of osteoblast induces osteoporosis and other bone metabolic diseases. The recent data have showed autophagy pathway plays an important role in osteoblast differentiation and activity. Hedgehog signalling pathway is required for osteoblast differentiation and development, and plays a crucial role in regulating both bone formation and autophagy, but Hh signalling mediated autophagy regulation in osteoblast has not yet been reported. So far, as an excellent bone model animal, zebrafish (Danio rerio ) shows high-throughput,rapidly,sensitively and high similarity with humans in terms of bone architecture, bone cells, matrix proteins, molecular signaling.So we will choose zebrafish as a model animal, to elucidate the role of autophagy pathway in osteoblast and the regulation of Hh signalling on autophagy,and investigate the interaction between Hh signaling and autophagy related genes. Furthermore,we will explore the regulation role of Hh-mediated autophagy in osteoblast and seek the cross talks among autophagy,Hh signalling and osteoblast development. We hope this study could help to find new molecular targets to treat osteoporosis and other bone diseases which resulted from osteoblast dysfunction.

成骨细胞负责骨形成，其功能失调会导致骨质疏松症等骨代谢疾病。最新数据显示自噬途径参与调控成骨细胞的分化与活性，但这种调控机制尚未研究清楚。Hedgehog（Hh）信号转导通路参与调节成骨细胞分化，影响骨形成，同时也是调控自噬的重要途径，但其介导的自噬在成骨细胞中调控作用未见报道。斑马鱼骨结构、骨细胞和分子信号与人类高度相似,高通量、快速、灵敏及方法学上的优势使其成为优秀的骨模型动物。因此本课题拟利用斑马鱼为模式动物，改变自噬水平和Hh信号水平，研究自噬途径对成骨细胞功能的影响和Hh信号对自噬途径的调节作用机制，并调查Hh信号和自噬基因间的交互作用。进一步研究Hh信号调低后，自噬水平对成骨细胞活性和分化的挽救作用，探索自噬途径、Hh信号和成骨细胞发育三者之间的相关性。希望能为发现治疗成骨细胞功能相关的骨质疏松症等骨代谢疾病的分子靶标提供新思路。