Effects Of Cyclic Tensile Strain On Proteoglycan Production And Signal Transduction Pathways In Intervertebral Disc Annulus Fibrosus Cells

BACKGROUNDLow back pain is a significant public health issue in our society, which accounts for much individual suffering and societal costs. Although there are multiple causes involved, degeneration of intervertebral disc has been implicated as the leading pathogenic process. Currently, the only available treatment modalities for disc-related low back pain focus on alleviating symptoms rather than addressing the underlying cause of degeneration. It is likely that clinical outcomes for patients with painful intervertebral disc degeneration would improve if therapies were developed that could slow, halt or reverse this process. While the factors that initiate and perpetuate disc degeneration are not well understood, it is a commonly held belief that disc degeneration is a multifactoral process involving both biochemical and biomechanical contributions. Within the disc, it is under overload from the forces of the muscles constrain motion and hydrostatic pressures at certain time, even at rest. Especially, annulus fibrosus (AF) cells are constantly subject to different stretch stresses in duration, intensity, and frequency in vivo. It is been shown in recent years that sensitivity to mechanical forces is a general property of all living tissues and all cultured cells. Many believe that disc degeneration has a cellular basis. So it is essential to study the effects of biomechanical stimulations on annulus fibrosus cells.Some evidence indicates that intervertebral disc degeneration begins with a progressive decrease in proteoglycan content. The major proteoglycan of the disc is aggrecan, which is thought to play a role in maintaining the collagen network and in collagen fibrillogenesis. Because aggrecan has a rapid turnover, the decreased production of aggrecan could significantly induce disc degeneration. Furthermore, researchers have shown that an autosomal recessive mutation in the aggrecan gene leads to intervertebral disc degeneration in mice. Taken together, it is shown that proteoglycan plays a main role in disc degeneration.