Defining the role of RANK in skeletal diseases associated with osteoclast dysfunction

NFkB受体激活因子（RANK）是细胞内分解骨骼的重要分子，称为破骨细胞。在一生中，破骨细胞与形成骨骼的细胞一起工作，保持骨骼健康和强壮。许多疾病发生时，破骨细胞不能正常工作，导致过多或不足的骨头被打破。这使得骨骼脆弱，容易骨折。我们正在研究影响婴儿、儿童和年轻人的罕见疾病，这些疾病是由RANK基因的变化引起的。这些疾病是骨质疏松症（由缺乏破骨细胞形成引起）和早发性Pagetic疾病（由破骨细胞过度活跃引起）。在实验室里，我们希望了解RANK分子的哪些部分对破骨细胞的形成和正常工作最重要。骨质疏松症是一种常见的疾病，过多的骨骼被分解，导致骨骼密度降低，脆弱，容易骨折，这导致了很多疼痛和不适。此外，与骨质疏松症治疗相关的医疗费用为每天600万美元。因此，重要的是我们要在人们的骨骼变得脆弱并开始骨折之前识别出有风险的人。我们将观察一组人的RANK基因，这些人的骨骼密度已经测量过，并确定基因中是否有任何变化可能与骨密度低的人有关。这些信息将被用来收集RANK变化的列表，如果存在，可以帮助预测哪些人可能患骨质疏松症。

Receptor Activator of NFkB (RANK) is an important molecule within cells that break down bone called osteoclasts. Throughout life, osteoclasts work together with cells that form bone to keep bones healthy and strong. Many diseases occur when osteoclasts do not work properly which leads to either too much or not enough bone being broken down. This makes the bones weak and easily fractured. We are studying rare diseases that affect babies, children and young adults and are caused by changes in the gene for RANK. These diseases are osteopetrosis (that is caused by a lack of osteoclast formation) and early-onset Pagetic diseases (that are caused by overactive osteoclasts). In the laboratory, we are hoping to learn about which parts of the RANK molecule are most important for osteoclasts to form and work properly. Osteoporosis is a common disease where too much bone is broken down leading to bones that are less dense, weak and fracture easily, which causes a lot of pain and discomfort. In addition, the healthcare costs associated with the treatment of osteoporosis are #6 million per day. It is therefore important that we identify people at risk before their bones become weak and start to fracture. We will look at the RANK gene in a group of people who have had the density of their bones measured and identify whether there are any changes in the gene that can be linked to people with low bone density. This information will then be used to assemble a list of changes within RANK that, if present, can help to predict which people are likely to develop osteoporosis.