Defects in intervertebral disc and spine during development, degeneration, and pain: New research directions for disc regeneration and therapy.

Q1 Biochemistry, Genetics and Molecular Biology Wiley Interdisciplinary Reviews: Developmental Biology Pub Date : 2019-07-01 Epub Date: 2019-04-11 DOI:10.1002/wdev.343
Sarthak Mohanty, Chitra L Dahia
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引用次数: 28

Abstract

Intervertebral discs are cartilaginous joints present between vertebrae. The centers of the intervertebral discs consist of a gelatinous nucleus pulposus derived from the embryonic notochord. With age or injury, intervertebral discs may degenerate, causing neurological symptoms including back pain, which affects millions of people worldwide. Back pain is a multifactorial disorder, and disc degeneration is one of the primary contributing factors. Recent studies in mice have identified the key molecules involved in the formation of intervertebral discs. Several of these key molecules including sonic hedgehog and Brachyury are not only expressed by notochord during development, but are also expressed by neonatal mouse nucleus pulposus cells, and are crucial for postnatal disc maintenance. These findings suggest that intrinsic signals in each disc may maintain the nucleus pulposus microenvironment. However, since expression of these developmental signals declines with age and degeneration, disc degeneration may be related to the loss of these intrinsic signals. In addition, findings from mouse and other mammalian models have identified similarities between the patterning capabilities of the embryonic notochord and young nucleus pulposus cells, suggesting that mouse is a suitable model system to understand disc development and aging. Future research aimed at understanding the upstream regulators of these developmental signals and the modes by which they regulate disc growth and maintenance will likely provide mechanistic insights into disc growth and aging. Further, such findings will likely provide insights relevant to the development of effective therapies for treatment of back pain and reversing the disc degenerative process.

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椎间盘和脊柱发育、退变和疼痛过程中的缺陷:椎间盘再生和治疗的新研究方向。
椎间盘是存在于椎骨之间的软骨关节。椎间盘的中心由源自胚胎脊索的胶状髓核组成。随着年龄增长或受伤,椎间盘可能退行性变,引起包括背痛在内的神经系统症状,影响全世界数百万人。背痛是一种多因素的疾病,椎间盘退变是主要因素之一。最近对小鼠的研究已经确定了参与椎间盘形成的关键分子。包括sonic hedgehog和Brachyury在内的一些关键分子不仅在脊索发育过程中表达,而且在新生小鼠髓核细胞中表达,并且对出生后的椎间盘维持至关重要。这些发现表明,每个椎间盘内的固有信号可能维持髓核微环境。然而,由于这些发育信号的表达随着年龄和退变而下降,椎间盘退变可能与这些内在信号的丧失有关。此外,来自小鼠和其他哺乳动物模型的研究结果发现,胚胎脊索和年轻髓核细胞的模式能力之间存在相似性,这表明小鼠是了解椎间盘发育和衰老的合适模型系统。未来的研究旨在了解这些发育信号的上游调节因子,以及它们调节椎间盘生长和维持的模式,这可能会为椎间盘生长和衰老提供机制上的见解。此外,这些发现可能会为开发治疗背痛和逆转椎间盘退变过程的有效疗法提供相关见解。本文分类如下:出生缺陷>器官异常脊椎动物器官发生>肌肉骨骼和血管成体干细胞,组织更新和再生>再生成体干细胞,组织更新和再生>干细胞和衰老。
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期刊介绍: Developmental biology is concerned with the fundamental question of how a single cell, the fertilized egg, ultimately produces a complex, fully patterned adult organism. This problem is studied on many different biological levels, from the molecular to the organismal. Developed in association with the Society for Developmental Biology, WIREs Developmental Biology will provide a unique interdisciplinary forum dedicated to fostering excellence in research and education and communicating key advances in this important field. The collaborative and integrative ethos of the WIREs model will facilitate connections to related disciplines such as genetics, systems biology, bioengineering, and psychology. The topical coverage of WIREs Developmental Biology includes: Establishment of Spatial and Temporal Patterns; Gene Expression and Transcriptional Hierarchies; Signaling Pathways; Early Embryonic Development; Invertebrate Organogenesis; Vertebrate Organogenesis; Nervous System Development; Birth Defects; Adult Stem Cells, Tissue Renewal and Regeneration; Cell Types and Issues Specific to Plants; Comparative Development and Evolution; and Technologies.
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