Degeneration and regeneration of the intervertebral disc: lessons from development.
Degeneration and regeneration of the intervertebral disc: lessons from development.
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DOI：
10.1242/dmm.006403
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发表时间：
2011-01
影响因子：
4.3
通讯作者：
Elliott DM
中科院分区：
文献类型：
--
作者：
Smith LJ;Nerurkar NL;Choi KS;Harfe BD;Elliott DM
椎间盘退变是一种以一系列细胞、生化、结构和功能变化为特征的过程，与下腰痛的原因密切相关。目前对腰椎间盘退变的治疗策略通常是针对下腰痛的症状，而不是治疗根本原因或恢复机械功能。通过考虑椎间盘发育的各个方面，可以对椎间盘退变以及治疗干预的机会有更深入的了解。椎间盘的发育涉及几种不同类型的细胞通过高度协调和复杂的分子相互作用而结合在一起。由此产生的结构必须在一个在个人一生中受到持续机械扰动的环境中协同发挥作用。出生后早期的变化，包括细胞性改变、血管退变和细胞外基质成分改变，可能会使椎间盘进入缓慢的症状性退化过程。在这一视角下，我们回顾了椎间盘退变的发病机制和治疗方法。在这个范围内，我们研究了模型系统如何促进我们对胚胎形态发生和相关的分子信号通路的理解，以及出生后对细胞、营养和机械微环境的变化。我们还讨论了促进椎间盘再生和修复的生物治疗策略的现状，以及从发展中吸取的经验教训如何为它们的改进提供线索。
Degeneration of the intervertebral discs, a process characterized by a cascade of cellular, biochemical, structural and functional changes, is strongly implicated as a cause of low back pain. Current treatment strategies for disc degeneration typically address the symptoms of low back pain without treating the underlying cause or restoring mechanical function. A more in-depth understanding of disc degeneration, as well as opportunities for therapeutic intervention, can be obtained by considering aspects of intervertebral disc development. Development of the intervertebral disc involves the coalescence of several different cell types through highly orchestrated and complex molecular interactions. The resulting structures must function synergistically in an environment that is subjected to continuous mechanical perturbation throughout the life of an individual. Early postnatal changes, including altered cellularity, vascular regression and altered extracellular matrix composition, might set the disc on a slow course towards symptomatic degeneration. In this Perspective, we review the pathogenesis and treatment of intervertebral disc degeneration in the context of disc development. Within this scope, we examine how model systems have advanced our understanding of embryonic morphogenesis and associated molecular signaling pathways, in addition to the postnatal changes to the cellular, nutritional and mechanical microenvironment. We also discuss the current status of biological therapeutic strategies that promote disc regeneration and repair, and how lessons from development might provide clues for their refinement.