Progranulin knockout accelerates intervertebral disc degeneration in aging mice.
Progranulin knockout accelerates intervertebral disc degeneration in aging mice.
复制标题
DOI：
10.1038/srep09102
复制
发表时间：
2015-03-16
影响因子：
4.6
通讯作者：
Liu CJ
中科院分区：
文献类型：
--
作者：
Zhao YP;Tian QY;Liu B;Cuellar J;Richbourgh B;Jia TH;Liu CJ
椎间盘退变是一种常见的退行性疾病，其发病机制尚不清楚。在此，我们研究了颗粒蛋白前体（PGRN），一种软骨保护生长因子，是否与IVD变性相关。PGRN在人和鼠IVD中都可检测到。在小鼠IVD组织中，PGRN水平在衰老过程中上调。PGRN的缺失导致IVD组织中退行性变化的早期发作和小鼠IVD组织中退行性相关分子的表达改变。此外，PGRN基因敲除小鼠表现出加速IVD基质变性，异常骨形成和过度的骨吸收在椎骨随着年龄的增长。在PGRN敲除小鼠中观察到的IVD变性的加速可能是由于NF-κB信号和β-catenin信号的增强激活。总而言之，PGRN可能在椎间盘的动态平衡中发挥关键作用，并可能成为预防和治疗椎间盘退行性疾病的潜在分子靶点。
Intervertebral disc (IVD) degeneration is a common degenerative disease, yet much is unknown about the mechanisms during its pathogenesis. Herein we investigated whether progranulin (PGRN), a chondroprotective growth factor, is associated with IVD degeneration. PGRN was detectable in both human and murine IVD. The levels of PGRN were upregulated in murine IVD tissue during aging process. Loss of PGRN resulted in an early onset of degenerative changes in the IVD tissue and altered expressions of the degeneration-associated molecules in the mouse IVD tissue. Moreover, PGRN knockout mice exhibited accelerated IVD matrix degeneration, abnormal bone formation and exaggerated bone resorption in vertebra with aging. The acceleration of IVD degeneration observed in PGRN null mice was probably due to the enhanced activation of NF-κB signaling and β-catenin signaling. Taken together, PGRN may play a critical role in homeostasis of IVD, and may serve as a potential molecular target for prevention and treatment of disc degenerative diseases.