MicroRNAs in Intervertebral Disc Degeneration, Apoptosis, Inflammation, and Mechanobiology

Abstract

Intervertebral disc (IVD) degeneration is a multifactorial pathological process associated with low back pain, the leading cause of years lived in disability worldwide. Key characteristics of the pathological changes connected with degenerative disc disease (DDD) are the degradation of the extracellular matrix (ECM), apoptosis and senescence, as well as inflammation. The impact of nonphysiological mechanical stresses on IVD degeneration and inflammation, the mechanisms of mechanotransduction, and the role of mechanosensitive miRNAs are of increasing interest. As post-transcriptional regulators, miRNAs are known to affect the expression of 30% of proteincoding genes and numerous intracellular processes. The dysregulation of miRNAs is therefore associated with various pathologies, including degenerative diseases such as DDD. This review aims to give an overview of the current status of miRNA research in degenerative disc pathology, with a special focus on the involvement of miRNAs in ECM degradation, apoptosis, and inflammation, as well as mechanobiology.

Keywords: ECM; MMP; annulus fibrosus; cartilaginous endplate; degenerative disc disease; miRNA; nucleus pulposus; senescence.

Figure 1

The role of microRNAs in the pathology of DDD. The miRNAs listed have been studied for their involvement in extracellular matrix (ECM) degradation, apoptosis, and inflammation, as well as mechanobiology as an overarching theme, respectively.

Figure 2

Overview of miRNAs associated with increased rates of apoptosis and senescence in DDD. Targets of negative miRNA regulation are shown in ellipses. The dysregulation of miRNAs and subsequently of their targets influence the downstream signaling, ultimately promoting apoptosis and senescence.