Shh signaling from the nucleus pulposus is required for the postnatal growth and differentiation of the mouse intervertebral disc.
Shh signaling from the nucleus pulposus is required for the postnatal growth and differentiation of the mouse intervertebral disc.
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DOI：
10.1371/journal.pone.0035944
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Wylie C
中科院分区：
文献类型：
--
作者：
Dahia CL;Mahoney E;Wylie C
椎间盘（IVD）是脊柱的重要组成部分。它们保持分离，并在相邻椎骨之间提供减震缓冲，同时还允许它们之间的运动。每个IVD由中央半液体髓核（NP）组成，周围是多层纤维软骨纤维环（AF）。虽然IVD在出生后沿着脊柱生长和分化，但对其机制知之甚少。了解控制正常IVD生长和分化的信号也将为退行性椎间盘疾病提供潜在的治疗方法，退行性椎间盘疾病是下背痛的主要原因，影响大部分人群。在这项工作中，我们表明，在小鼠出生后的生长过程中，来自NP细胞的Sonic hedgehog（Shh）信号控制NP细胞本身和周围AF的生长和分化的许多方面，并且它至少部分地通过调节NP和AF中的其他信号通路起作用。最近的研究表明，NP细胞起源于胚胎脊索，它是胚胎中的主要信号中心。这项工作表明，这种脊索来源的组织继续在出生后的身体中执行主要的信号功能，并且除了它们在脊柱功能力学中已知的功能之外，IVD是信号中心。
Intervertebral discs (IVD) are essential components of the vertebral column. They maintain separation, and provide shock absorbing buffers, between adjacent vertebrae, while also allowing movements between them. Each IVD consists of a central semi-liquid nucleus pulposus (NP) surrounded by a multi-layered fibrocartilagenous annulus fibrosus (AF). Although the IVDs grow and differentiate after birth along with the vertebral column, little is known about the mechanism of this. Understanding the signals that control normal IVD growth and differentiation would also provide potential therapies for degenerative disc disease, which is the major cause of lower back pain and affects a large proportion of the population. In this work, we show that during postnatal growth of the mouse, Sonic hedgehog (Shh) signaling from the NP cells controls many aspects of growth and differentiation of both the NP cells themselves and of the surrounding AF, and that it acts, at least partly, by regulating other signaling pathways in the NP and AF. Recent studies have shown that the NP cells arise from the embryonic notochord, which acts as a major signaling center in the embryo. This work shows that this notochord-derived tissue continues to carry out a major signaling function in the postnatal body and that the IVDs are signaling centers, in addition to their already known functions in the mechanics of vertebral column function.
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