Genetic Factors in Intervertebral Disc Degeneration

Abstract

Low back pain (LBP) is a major cause of disability and imposes huge economic burdens on human society worldwide. Among many factors responsible for LBP, intervertebral disc degeneration (IDD) is the most common disorder and is a target for intervention. The etiology of IDD is complex and its mechanism is still not completely understood. Many factors such as aging, spine deformities and diseases, spine injuries, and genetic factors are involved in the pathogenesis of IDD. In this review, we will focus on the recent advances in studies on the most promising and extensively examined genetic factors associated with IDD in humans. A number of genetic defects have been correlated with structural and functional changes within the intervertebral disc (IVD), which may compromise the disc's mechanical properties and metabolic activities. These genetic and proteomic studies have begun to shed light on the molecular basis of IDD, suggesting that genetic factors are important contributors to the onset and progression of IDD. By continuing to improve our understanding of the molecular mechanisms of IDD, specific early diagnosis and more effective treatments for this disabling disease will be possible in the future.

Keywords: Genetic factor; Intervertebral disc; Intervertebral disc degeneration; Low back pain; Polymorphism.

Figure 1

(A) Left panel: An illustration shows a cut out portion of a normal disc. Note the relationships between nucleus pulposus, annulus fibrosus, and vertebral endplate. Right panel: An enlargement of NP part of the disc. The NP contains collagen fibers and elastin fibers, both of which are embedded in highly hydrated aggrecan-containing gel. The NP also contains numerous chondrocyte-like cells with dark round nuclei as well as a relatively small number of fibroblasts with elongated nuclei. The chondrocyte-like cells usually exhibit close spatial groupings and are arranged either in rows among the collagen fibers or in isogenous group. (B) Illustrations showing normal and degenerated intervertebral disc (IVD). The central nucleus pulposus is enclosed by outer annulus fibrosus. When degeneration occurs, the nucleus pulposus becomes more fibrotic and less gel-like, while the annulus fibrosus becomes irregular and disorganized. Cleft formation can be observed, especially in the nucleus pulposus (arrow head), which can even be pushed out beyond the boundary of the disc due to deterioration of the annulus fibrosus (arrow).

Figure 2

Intervertebral disc degeneration can be attributed to many different factors, including genetic factors as well as aging, injury, spine deformity (e.g. scoliosis and kyphosis). These biological and environmental factors may lead to the spine being susceptible to stress and abnormal gene expression. As a result, increased catabolic activity and decreased anabolic activity may occur in the intervertebral disc, leading to intervertebral disc degeneration.