Molecular therapy of the intervertebral disc

Abstract

Disc degeneration is the loss of the normal nucleus pulposus disc matrix to a more fibrotic and less cartilaginous structure. This change in disc micro-anatomy can be associated with pain and deformity, however, prevention and treatment options of disc degeneration are currently limited. Much research is going on to understand intervertebral discs at a molecular/ cellular level in hopes of creating clinically applicable options for treating disc degeneration. This review article will give insight into the current and developing status of treating intervertebral disc degeneration from a molecular standpoint.

Fig. 1

Disc-matrix metabolism: balance of synthesis and degradation. a In the homeostatic state, the disc undergoes matrix synthesis and degradation in a balanced manner. b As the disc matrix undergoes a turnover during the course of an individual’s lifetime, any small imbalance between synthesis and degradation can lead to significant changes in overall disc-matrix content. c One of the major goals of molecular therapy of the disc involves modulating this metabolic balance to the more favorable anabolic state. This can be accomplished by increasing the synthesis or decreasing the catabolism

Fig. 2

Mitogenic molecules: mitogenic molecules are the true growth factors. They increase the cell number without necessarily enhancing cell differentiation. The increase in cell number leads to increase in matrix synthesis. However, this may also increase the nutritional requirement in the disc due to higher needs for keeping the cell alive and perhaps increase the overall catabolism as well as synthesis. Furthermore, high cell density can lead to less nutrition per cell leading to limits on synthetic metabolism. Finally, mitogens may have a potential to promote tumors

Fig. 3

Morphogenic molecules: morphogens change the phenotype of the cell as their major mechanism of action without necessarily increasing the cell number. In the disc, morphogens may be used to increase the chondrocyte-like phenotype of the cells and enhance chondrocytic matrix synthesis

Fig. 4

Intracellular regulators: intracellular regulatory are not secreted molecules and do not act through a transmembrane receptor. Intracellular regulators can induce the secretion of cytokines to act in autocrine or paracrine fashion or directly up-regulate matrix production