Developments in intervertebral disc disease research: pathophysiology, mechanobiology, and therapeutics

Abstract

Low back pain is a leading cause of disability worldwide and the second most common cause of physician visits. There are many causes of back pain, and among them, disc herniation and intervertebral disc degeneration are the most common diagnoses and targets for intervention. Currently, clinical treatment outcomes are not strongly correlated with diagnoses, emphasizing the importance for characterizing more completely the mechanisms of degeneration and their relationships with symptoms. This review covers recent studies elucidating cellular and molecular changes associated with disc mechanobiology, as it relates to degeneration and regeneration. Specifically, we review findings on the biochemical changes in disc diseases, including cytokines, chemokines, and proteases; advancements in disc disease diagnostics using imaging modalities; updates on studies examining the response of the intervertebral disc to injury; and recent developments in repair strategies, including cell-based repair, biomaterials, and tissue engineering. Findings on the effects of the omega-6 fatty acid, linoleic acid, on nucleus pulposus tissue engineering are presented. Studies described in this review provide greater insights into the pathogenesis of disc degeneration and may define new paradigms for early or differential diagnostics of degeneration using new techniques such as systemic biomarkers. In addition, research on the mechanobiology of disease enriches the development of therapeutics for disc repair, with potential to diminish pain and disability associated with disc degeneration.

Fig. 1

Biomarkers of disc degeneration and back pain. Disc degeneration process begins years before disc height narrowing is observable by current diagnostic methods (structural, radiological). There is an urgent need for earlier methods of detection of disc degeneration, which can lead to novel and earlier, less invasive therapies

Fig. 2

Temporal effects of TGF-β and LA on NP Cells. a NP cells were cultured in 2 % agarose hydrogels for up to 42 days in culture. Bars indicate duration of exposure. b Percent increase in equilibrium modulus from day 14 values measured by unconfined compression tests. *p < 0.001 versus all other groups. c Percent increase in GAG content per wet weight of NP constructs from day 14 values. *p < 0.001 versus respective LA− group. ⁺ p < 0.002 versus LA−/TGF+