Ghrelin在青少年特发性脊柱侧凸骨骼异常发育中的作用及分子机制研究

青少年特发性脊柱侧弯（AIS）发病率、致残率高，其发病机制迄今未明。现有研究显示：AIS患者中存在多种激素水平紊乱，其中，胃饥饿素（Ghrelin）在AIS患者中显著升高，但其对脊柱生长的调控作用鲜有研究；Ghrelin对骨形成起到重要的调控作用，它能够促进软骨细胞代谢，且对成骨细胞分化和细胞功能有影响。我们前期研究发现，AIS患者原代细胞系对Ghrelin反应相比正常人存在差异。据此，我们推测Ghrelin在AIS发病中可能起到重要作用。在本研究中，我们计划从Ghrelin对软骨细胞代谢、成骨细胞分化、成骨细胞及破骨细胞功能的影响入手，应用AIS患者及健康对照的原代细胞系、基因敲除小鼠、成骨细胞系等模型，探索在AIS中，Ghrelin对软骨细胞功能、成骨分化及成骨功能存在差异影响的具体机制，以便从整体水平探讨Ghrelin在AIS中介导脊柱异常发育的机制。

Adolescent idiopathic scoliosis (AIS) is a disease with unknown aetiology, high rates of morbidity and disability. Previous studies have shown that there are various hormone level disturbances in AIS patients. Ghrelin is one of those hormones which significantly increased in AIS, but its regulation of spinal growth rarely studied. Ghrelin plays an important role in the regulation of bone formation. It can affect the metabolic rate of chondrocytes, osteoblast differentiation and osteoblast function. Our previous study found that primary cells from AIS patients have different response to Ghrelin, compared to normal people. Accordingly, we hypothesize that Ghrelin may play an important role in the pathogenesis of AIS. In this study, we planned to investigate the effects of Ghrelin on chondrocyte metabolism, osteoblast differentiation, osteoblasts and osteoclast function in AIS, by using primary cell lines from AIS patients and healthy controls, knockout mice, bone cell lines. We aim to explore the mechanism of Ghrelin mediated spine abnormal growth in AIS from the whole level.