Degeneration and regeneration of the intervertebral disc: lessons from development

Abstract

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.

Association between the Number of Chondrocytes of Lumbar Intervertebral Discs and Age, Abdominal Aorta Atherosclerosis and Lumbar Artery Arteriosclerosis Descriptive Cross Sectional Study

“…According to Smith et al disc degeneration increases with age [9]. Takatalo et al demonstrates that intervertebral disc degeneration increases with advanced atherosclerotic manifestations in the abdominal aorta [11].…”

“…A key factor in early disc degeneration is the decrease in proteoglycan content. [9]. During intervertebral disc degeneration (IVD), chondrocytes respond to early degeneration by increasing their biosynthetic processes [6].…”

Low back pain: possibilities of pathogenetic treatment

“…Потеря гидрофильных молекул матрикса приводит к структурным изменениям и нестабильности позвонков, что рассматривается как основная причина протрузии дисков, радикулопатии и, возможно, спинального стеноза [7,8]. Важнейшим фактором формирования дегенератив-ных изменений является разрыв фиброзного кольца МПД [9,10]. Многочисленные исследования, между тем, де-монстрируют, что определяемые гистологически и на МРТ разрывы фиброзного кольца дисков у пациентов с БНС не могут рассматриваться как надежный маркер формирования болевых проявлений.…”

“…Здесь они взаимодействуют с ноцицептивными рецепторами и способствуют прораста-нию нервных волокон через разрывы внутрь фиброзного кольца вплоть до структур пульпозного ядра, что в сово-купности и вызывает БНС [22,23]. Разрывы фиброзного кольца -частый феномен в процессе дегенерации дисков [9,10]. Нервные волокна имеют тенденцию распростра-няться вдоль фиброзного кольца во внутреннюю его часть, даже в ткани пульпозного ядра.…”

Characteristics of Stem Cells Derived from the Degenerated Human Intervertebral Disc Cartilage Endplate

“…Therefore, therapies that both alleviate painful symptoms and restore disc structure and mechanical function by directly addressing the underlying biological causes of disc degeneration are needed [15]. Recently, cell-based therapies for regenerating or repairing the disc have become treatment options [15,16].…”