Mechanobiology of the Human Intervertebral Disc: Systematic Review of the Literature and Future Perspectives

Abstract

Low back pain is an extremely common condition with severe consequences. Among its potential specific causes, degenerative disc disease (DDD) is one of the most frequently observed. Mechanobiology is an emerging science studying the interplay between mechanical stimuli and the biological behavior of cells and tissues. The aim of the presented study is to review, with a systematic approach, the existing literature regarding the mechanobiology of the human intervertebral disc (IVD), define the main pathways involved in DDD and identify novel potential therapeutic targets. The review was carried out in accordance with the Preferential Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Studies were included if they described biological responses of human IVD cells under mechanical stimulation or alterations of mechanical properties of the IVD determined by different gene expression. Fifteen studies were included and showed promising results confirming the mechanobiology of the human IVD as a key element in DDD. The technical advances of the last decade have allowed us to increase our understanding of this topic, enabling us to identify possible therapeutic targets to treat and to prevent DDD. Further research and technological innovations will shed light on the interactions between the mechanics and biology of the human IVD.

The Role of Mechanotransduction in Contact Inhibition of Locomotion and Proliferation

“…Although this article presented several instances of mechanical force involvement in biological processes, the precise molecular mechanism underlying how these forces are sensed and translated into biochemical signals remained unclear at the time. Over the past two decades, the field has made considerable progress, and more recent review articles have been published focusing on mechanotransduction in human diseases [17,18,[259][260][261][262]. As presented in Table S1, numerous cell densityand mechano-sensitive proteins have been identified, and ongoing research is exploring the molecular regulation of these molecules.…”

Anti-Inflammatory Effects of Adiponectin Receptor Agonist AdipoRon against Intervertebral Disc Degeneration

“…Although numerous factors may initiate IVD degeneration, the imbalance of ECM metabolism, inflammatory response, apoptosis, and autophagy play essential roles in promoting the development of disc degeneration for molecular response [7,32,33]. In addition, mechanobiology, the new science that studies the interaction between mechanical stimuli and the biological behavior of cells and tissues, has been attracting attention in recent years as a key element in degenerative disc disease, and has led to the study of intervertebral disc degeneration [34]. TNF-α is a highly potent inflammatory cytokine and a pivotal contributor to IVD degeneration by participating in ECM degradation, inflammatory response, cell senescence, autophagy, and apoptosis [35,36].…”

Contact Inhibition and Mechanotransduction

“…Although this article presented several instances of mechanical force involvement in biological processes, the precise molecular mechanism underlying how these forces are sensed and translated into biochemical signals remained unclear at that time. Over the past two decades, the field has made considerable progress, and more recent review articles have been published, focusing on mechanotransduction in human diseases [16,17,[246][247][248][249]. As presented in Table S1, numerous cell density-and mechano-sensitive proteins have been identified, and ongoing research is exploring the molecular regulation of these molecules.…”