Department of Orthopaedic Surgery, Thomas Jefferson University, College of Medicine, Philadelphia, PA, USA.
Spine (Phila Pa 1976). 2011 Apr 15;36(8):E513-8. doi: 10.1097/BRS.0b013e3181f52cb5.
Histologic analysis of intervertebral disc (IVD) in three types of transgenic mice.
To investigate the role of Wnt/β-catenin signaling in regulation of IVD development and organization.
β-catenin dependent Wnt signaling is one of the central regulators in cartilage development during limb skeletal formation. Little is known, however, about the physiologic relevance of this signaling pathway to IVD development and organization.
Temporal-spatial distribution of Wnt/β-catenin signaling activity was examined in IVD using Wnt/β-catenin reporter (TOPGAL) mice. The structural changes in the mouse IVD components such as the nucleus pulposus (NP), endplate (EP), annulus fibrosus (AF), and the growth plate (GP) of the vertebral body were analyzed after transient activation of Wnt/β-catenin signaling or deletion of β-catenin in the mice.
Activity of Wnt/β-catenin signaling was high in EP, AF, and GP in the embryonic stages and decreased at the postnatal stage; it was undetectable in the embryonic NP but upregulated after birth. The transient activation of Wnt/β-catenin signaling caused severe deterioration of the GP and the AF, whereas deficiency of β-catenin accelerated bone formation in between EP and GP.
The findings in this study suggest that proper regulation of Wnt/β-catenin signaling is required for development and organization of IVD.
对三种转基因小鼠的椎间盘（IVD）进行组织学分析。
研究 Wnt/β-catenin 信号通路在调节 IVD 发育和组织中的作用。
β-catenin 依赖性 Wnt 信号通路是肢体骨骼形成过程中软骨发育的核心调节因子之一。然而，关于该信号通路与 IVD 发育和组织的生理相关性知之甚少。
使用 Wnt/β-catenin 报告基因（TOPGAL）小鼠检测 IVD 中 Wnt/β-catenin 信号活性的时空分布。在小鼠中短暂激活 Wnt/β-catenin 信号或敲除 β-catenin 后，分析椎间盘各组成部分（如髓核、终板、纤维环和椎体生长板）的结构变化。
在胚胎期，Wnt/β-catenin 信号活性在终板、纤维环和生长板中较高，在出生后阶段降低；在胚胎期髓核中无法检测到，但出生后上调。Wnt/β-catenin 信号的短暂激活导致生长板和纤维环严重恶化，而β-catenin 的缺失加速了终板和生长板之间的骨形成。
本研究结果表明，适当调节 Wnt/β-catenin 信号通路对于 IVD 的发育和组织至关重要。
