The zebrafish mutant droog as a model for human osteoporosis

描述(由申请人提供)：在日益增长的老年人口中，骨质疏松症造成的骨折是一个重大的公共健康负担，高昂的医疗费用，以及降低的生活质量。据估计，40-90%的骨密度变异可能是由于遗传变异造成的。尽管已发现40多个骨质疏松症的候选基因，但由于大量的基因在骨发育和动态平衡中起作用，这些候选基因在人群水平上只占骨密度遗传变异的不到1%。这些研究确定骨质疏松症是一个主要的健康问题，并强调需要进一步的研究和更好的动物模型来阐明这种疾病背后的遗传因素。在拟议的研究中，我们将确定新发现的斑马鱼骨质疏松症突变体Droog(Dro)tft92N的分子和发育性质，作为一种新的人类骨质疏松症动物模型。这项研究具有重要意义和创新性，因为它可能为预防骨质疏松症提供一个新的基因。此外，这些研究将验证斑马鱼突变体dro作为一种新的模型，以提高我们对导致人类骨质疏松症的遗传因素的理解，并作为体内筛选工具来确定治疗人类骨质疏松症的新治疗靶点。我们提出的建立三维(3D)体外细胞培养模型来研究正常和dro突变收获的细胞的研究，将为小分子筛选提供一个创新的平台，以确定改进和有效治疗人类骨质疏松症的新疗法。

DESCRIPTION (provided by applicant): Bone fractures due to osteoporosis present a significant public health burden, high medical costs, and reduced quality of life in an increasingl aged population. It is estimated that 40-90% of variation in BMD may be due to genetic variability. Although more than 40 candidate genes for predisposition to osteoporosis have been identified, they represent less than 1% of the genetic variance of BMD at the population level, due to the large number of genes functioning in bone development and homeostasis. These studies identify osteoporosis as a major health problem, and emphasize the need for further research and better animal models to elucidate genetic factors underlying this disease. In the proposed studies, we will define the molecular and developmental nature of the newly identified zebrafish osteopenia mutant, droog(dro)tft92N, as a novel animal model for human osteoporosis. This research is significant and innovative in that it may implicate a new gene in the prevention of osteoporosis. In addition, these studies will validate the zebrafish mutant dro as a new model to improve our understanding of the genetic contributions leading to human osteoporosis, and as an in vivo screening tool to identify new therapeutic targets to treat human osteoporosis. Our proposed studies to establish a three dimensional (3D) in vitro cell culture model to study normal and dro mutant harvested cells will provide an innovative platform for small molecular screens to identify novel therapies for improved and effective treatment of human osteoporosis.