A computational model for investigating the effects of changes in bioavailability of insulin-like growth factor-1 on the homeostasis of the intervertebral disc

In this study, it was found that IGF-1 deficiency mainly affects the biosynthesis of ECM components, especially in the most external regions of the IVD such as the cartilage endplates and the outer portion of annulus fibrosus. Also, a total of three approaches for increasing IGF-1 bioavailability as a therapy for degenerated IVDs were investigated. It was found that all these strategies are only beneficial to those disc regions receiving sufficient nutritional supply (i.e., the outmost IVD regions), while they exacerbate tissue degradation in malnourished regions (i.e., inner portion of the disc). This suggests that pro-anabolic growth factor-based therapies are limited in that their success strongly depends on an adequate nutritional supply to the IVD tissue, which is not guaranteed in degenerated discs.