纳米羟基磷灰石复合物通过Bmp信号通路促进斑马鱼骨骼发育的功能与机制研究

项目名称： 纳米羟基磷灰石复合物通过Bmp信号通路促进斑马鱼骨骼发育的功能与机制研究

项目编号： No.31501174

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 生物科学

项目作者： 薛钰

作者单位： 闽南师范大学

项目金额： 20万元

中文摘要： 羟基磷灰石是脊椎动物骨骼和牙齿的主要无机成分，人工合成的纳米羟基磷灰石由于其良好的生物活性常被作为生物材料用于骨组织修复。然而其在促进骨骼发育中的作用机理还有待进一步研究。我们从双孢蘑菇中首次发现并提取纯化出天然的纳米羟基磷灰石复合成分，前期的研究结果表明，该复合物能有效修复小鼠的齿骨损伤；斑马鱼中，纳米羟基磷灰石复合物能引起胚胎发育晚期明显的腹部化表型，并使bmp2b、bmp4 mRNA 在背部神经嵴的表达上调。由于Bmp信号通路在斑马鱼骨骼发育过程中具有重要作用，因此我们推测纳米羟基磷灰石复合物可能通过Bmp信号促进骨骼生长。本项目拟进一步分析纳米级羟基磷灰石复合物对斑马鱼骨骼发育的影响；阐明纳米级羟基磷灰石复合物与Bmp信号的相互作用关系和调控机制；探讨纳米级羟基磷灰石复合物通过Bmp信号调控骨骼发育的分子机理。以加深对这类天然小分子化合物在促进骨骼发育中的调控机制的理解。

中文关键词： 纳米羟基磷灰石；Bmp信号通路；骨骼发育；斑马鱼

英文摘要： Hydroxyapatite(HA) is the major inorganic component of bone and teeth in vertebrates, synthetic nano-hydroxyapatite has became a common biomaterial for bone repair and regeneration as its well-known bioactivity. However, the molecular mechanism of nano- hydroxyapatite in promoting skeletal development remains largely unknown. Recently, we identified firstly and purified the natural nano-hydroxyapatite compound from Agaricus bisporus. Our preliminary studies showed that this compound had demonstrable effect for injured teeth repair in mouse. In zebrafish model, nano-hydroxyapatite compound caused obvious embryonic ventralization at late developmental stage, and greatly increased bmp2b and bmp4 mRNA expression level in neural crest. Since Bmp/Smads signal pathway plays an essential role during osteogenesis, we suppose that nano-hydroxyapatite compound may regulate skeletal development through Bmp signal. In this study, we will furtherly explore molecular mechanisms in the control of Bmp pathway by nano-hydroxyapatite compound, and uncover the novel role of this compound on the skeletal development in zebrafish. These results will provide new insights into the regulation mechanisms of this kind of compound which promotes bone formation during development.

英文关键词： Nano-hydroxyapatite;Bmp signal pathway;skeletal development;zebrafish