Age-related changes in the intervertebral disk.

描述（由申请人提供）：位于每个椎骨之间的椎间盘退化在老年脊椎动物中很常见。腰椎间盘相关的变化被认为是导致大多数背痛的原因。背痛几乎影响着每个人一生中的某个阶段，每年有150万人致残。椎间盘的中心区域由称为髓核的柔软、高度水合的组织组成。脱水或髓核损伤会导致椎间盘之间的负荷转移效率低下，导致椎间盘突出和其他类型的椎间盘疾病。没有治疗磁盘损伤/退化的方法。hedgehog和Bmp信号通路都与许多组织的形成和出生后的维持有关，但是研究椎间盘中这些重要信号通路的功能所需的工具还没有。在这个提议中，我们将使用新的小鼠染色和我们最近开发的技术来测试我们的假设，即刺猬和BMP信号通路的改变是年龄相关的椎间盘退变的原因。在目标1中，将检查刺猬信号在椎间盘发育和维持中的作用。目的2将研究特定的刺猬家族成员Shh在胚胎后维持健康椎间盘中的作用。在目标3中，我们提出从椎间盘中去除在刺猬信号传导下游起作用的BMP蛋白的组合，以研究我们的假设，即BMP蛋白对椎间盘细胞的刺激不足导致椎间盘退变。

DESCRIPTION (provided by applicant): Deterioration of the intervertebral disks, located between each vertebra, is common in older vertebrates. Age-related changes in the intervertebral disks are thought to cause most cases of back pain. Back pain affects nearly everyone at some point of their lives, with 1.5 million people a year becoming disabled. The center region of the intervertebral disk is composed of soft, highly hydrated tissue called the nucleus pulposus. Dehydration or damage to the nucleus pulposus can result in inefficient transfer of load between the intervertebral disks, leading to disk herniation and other types of disk disease. There are no cures for disk damage/degeneration. Both the hedgehog and Bmp signaling pathways have been implicated in the formation and postnatal maintenance of a number of tissues, however the tools necessary to investigate the function of these important signaling pathways in the intervertebral disks have not been available. In this proposal, we will use novel mouse stains and techniques we have recently developed to test our hypothesis that alterations in hedgehog and Bmp signaling pathways are responsible for age-related disk degeneration. In Aim 1, the role of hedgehog signaling in the development and maintenance of the intervertebral disks will be examined. Aim 2 will investigate the role a specific hedgehog family member, Shh, plays in the postembryonic maintenance of healthy intervertebral disks. In Aim 3, we propose to remove combinations of Bmp proteins, which function downstream of hedgehog signaling, from the intervertebral disks to investigate our hypothesis that inadequate stimulation of intervertebral disk cells by Bmp proteins results in disk degeneration.