Intervertebral disc development is regulated by Wnt/β-catenin signaling.
Intervertebral disc development is regulated by Wnt/β-catenin signaling.
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DOI：
10.1097/brs.0b013e3181f52cb5
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发表时间：
2011-04-15
期刊：
影响因子：
3
通讯作者：
Enomoto-Iwamoto M
中科院分区：
文献类型：
--
作者：
Kondo N;Yuasa T;Shimono K;Tung W;Okabe T;Yasuhara R;Pacifici M;Zhang Y;Iwamoto M;Enomoto-Iwamoto M
三种转基因小鼠椎间盘（IVD）的组织学分析。研究 Wnt/β-catenin 信号在 IVD 发育和组织调节中的作用。 β-连环蛋白依赖性 Wnt 信号传导是肢体骨骼形成过程中软骨发育的中心调节因子之一。然而，人们对这一信号通路与 IVD 发育和组织的生理相关性知之甚少。使用 Wnt/β-连环蛋白报告基因 (TOPGAL) 小鼠在 IVD 中检查 Wnt/β-连环蛋白信号活性的时空分布。在小鼠中短暂激活 Wnt/β-catenin 信号或删除 β-catenin 后，分析了小鼠 IVD 组件的结构变化，例如椎体的髓核 (NP)、终板 (EP)、纤维环 (AF) 和生长板 (GP)。胚胎期EP、AF和GP中Wnt/β-catenin信号活性较高，出生后活性降低；它在胚胎 NP 中检测不到，但在出生后上调。 Wnt/β-连环蛋白信号的瞬时激活导致 GP 和 AF 严重恶化，而 β-连环蛋白的缺乏则加速 EP 和 GP 之间的骨形成。本研究的结果表明，IVD 的发展和组织需要适当调节 Wnt/β-catenin 信号传导。
Histological 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 physiological 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 following 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 up-regulated 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.