Role of Autophagy and Pyroptosis in Intervertebral Disc Degeneration

Abstract

Intervertebral disc degeneration is a chronic degenerative disease caused by the interaction of genetic and environmental factors, mainly manifested as lower back pain. At present, the diagnosis of intervertebral disc degeneration mainly relies on imaging. However, early intervertebral disc degeneration is usually insidious, and there is currently a lack of relevant clinical biomarkers that can reliably reflect early disease progression. Pyroptosis is a regulatory form of cell death triggered by the activation of inflammatory bodies and caspase, which can induce the formation of plasma membrane pores and cell swelling or lysis. Previous studies have shown that during the progression of intervertebral disc degeneration, sustained activation of inflammasomes leads to nuclear cell pyroptosis, which can occur in the early stages of intervertebral disc degeneration. Moreover, intervertebral disc nucleus pulposus cells adapt to the external environment through autophagy and maintain cellular homeostasis and studying the mechanism of autophagy in IDD and intervening in its pathological and physiological processes can provide new ideas for the clinical treatment of IDD. This review analyzes the effects of pyroptosis and autophagy on IDD by reviewing relevant literature in recent years, in order to explore the relationship between pyroptosis, autophagy and IDD.

Keywords: autophagy; intervertebral disc degeneration; pyroptosis.

Figure 1

The Physiological structure of IVDD. The cell density of gel shaped nucleus pulposus tissue is low, and the extracellular matrix mainly includes type II collagen and proteoglycan. Protein polysaccharides (mainly aggregated proteoglycans and hyaluronic acid) can maintain intervertebral disc moisture, maintain disc height, and buffer axial loads on the spine. The fibrous ring is the fibrous tissue surrounding the nucleus pulposus, consisting of two layers: 1) the inner fibrous ring, and 2) the outer fibrous ring. The outer fibrous ring plays an important role in maintaining the integrity of intervertebral discs. The cartilage endplate contains abundant type II collagen and chondrocytes, which attach the intervertebral disc to the vertebral body and provide nutrients for the intervertebral disc. Blood vessels and nerves are only distributed in the outer fibrous ring of the intervertebral disc in healthy adults. Nutrients passively diffuse to the deep nucleus pulposus. The nerves in the scar in the degenerative intervertebral disc are the main cause of discogenic pain.

Figure 2

Risk factors for IVDD. Smoking, aging, genetics and mechanics related diseases also further accelerate IVDD.