Current information regarding the biochemical and genetic events that occur during disc degeneration

Intervertebral disc degeneration is a significant health care problem in western societies. Degeneration results in changes to the composition and the characteristics of the disc. Decreased proteoglycan and collagen levels occur in the extracellular matrix of the nucleus pulposus, and the cell count and cell distribution are affected as well. Recent biochemical studies have shown that proteoglycan production is decreased in these discs. Additionally, levels of the enzymes capable of degrading collagen and proteoglycans were found to be elevated in degenerative discs, especially at the location of ongoing degeneration. Genetic investigations have supported these findings. Although more studies are needed to delineate further the interactions occurring during intervertebral disc degeneration, these biochemical and genetic studies have begun to give insight into the molecular causes of disc degeneration. Although disc degeneration in the lumbar spine is an important source of low back pain and associated health problems, the underlying causes of degeneration of the intervertebral disc (IVD) remain unclear. Disc degeneration is likely the result of a complex interaction of aging, biomechanical stress, biochemical changes, and genetic aberrations. The IVD is composed of two main parts: the nucleus pulposus (NP) and the annulus fibrosus (AF). The NP consists of a cellular component and an extracellular matrix (ECM), mainly type II collagen and proteoglycans (PGs). The most common PG is aggrecan [1], but smaller amounts of other PGs are present as well. These PGs create a hydrophilic environment, leading to fluid retention and swelling of the NP. Surrounding the NP is the AF, consisting primarily of type I collagen, with lesser amounts of types II and III. The AF serves to contain the NP and to bind adjacent vertebrae. The normal IVD allows multiple planes of motion while resisting the compressive forces to which the spine is subjected daily. Disc degeneration changes the composition of the IVD. Previous work has helped elucidate the structural changes seen in degeneration [2•,3–7]. With aging, the organized collagen bundles of the AF become increasingly more irregular. Additionally, the interface between the NP and AF becomes less clear. The NP undergoes changes in both its cellular components and the ECM. The amount, types, and proportions of collagen and PGs change. Clefts and tears develop in the matrix, and the number and location of cells differ from healthy IVDs. Recently, the ultrastructural changes of the degenerating disc have been delineated [8]. Changes include widened collagen fibrils, fibrous long-spacing collagen, and irregular fibril diameters. Degenerative disc cells show characteristic findings of apoptosis and are encircled by layers of ECM. These structural and ultrastructural changes likely lead to the compromised biomechanical function of the degenerating disc. The underlying causes of these structural changes, however, remain elusive. The interaction between the disc cells and the ECM is complex and is likely altered during degeneration. Much current work revolves around clarifying the biochemical and genetic changes that occur during disc degeneration.