Division of Orthopaedic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America.
The Perinatal Institute Division of Neonatology, Perinatal and Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America.
PLoS One. 2014 Jun 3;9(6):e98444. doi: 10.1371/journal.pone.0098444. eCollection 2014.
Intervertebral discs (IVDs) are strong fibrocartilaginous joints that connect adjacent vertebrae of the spine. As discs age they become prone to failure, with neurological consequences that are often severe. Surgical repair of discs treats the result of the disease, which affects as many as one in seven people, rather than its cause. An ideal solution would be to repair degenerating discs using the mechanisms of their normal differentiation. However, these mechanisms are poorly understood. Using the mouse as a model, we previously showed that Shh signaling produced by nucleus pulposus cells activates the expression of differentiation markers, and cell proliferation, in the postnatal IVD. In the present study, we show that canonical Wnt signaling is required for the expression of Shh signaling targets in the IVD. We also show that Shh and canonical Wnt signaling pathways are down-regulated in adult IVDs. Furthermore, this down-regulation is reversible, since re-activation of the Wnt or Shh pathways in older discs can re-activate molecular markers of the IVD that are lost with age. These data suggest that biological treatments targeting Wnt and Shh signaling pathways may be feasible as a therapeutic for degenerative disc disease.
椎间盘（IVD）是连接脊柱相邻椎骨的强纤维软骨关节。随着椎间盘的老化，它们容易出现故障，导致严重的神经后果。椎间盘的手术修复治疗的是这种疾病的结果，这种疾病影响多达七分之一的人，而不是其病因。理想的解决方案是利用椎间盘正常分化的机制来修复退化的椎间盘。然而，这些机制还不太清楚。我们之前曾使用小鼠作为模型，表明来自髓核细胞的 Shh 信号激活了出生后椎间盘的分化标志物的表达和细胞增殖。在本研究中，我们表明经典 Wnt 信号通路是椎间盘中 Shh 信号靶标的表达所必需的。我们还表明，成年椎间盘中 Shh 和经典 Wnt 信号通路的表达下调。此外，这种下调是可逆的，因为在较老的椎间盘中重新激活 Wnt 或 Shh 通路可以重新激活随年龄增长而丢失的 IVD 分子标志物。这些数据表明，针对 Wnt 和 Shh 信号通路的生物治疗可能是退行性椎间盘疾病的一种可行的治疗方法。
