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Role of Autophagy in Intervertebral Disc Degeneration

June 7, 2022

Gwendolyn Sowa, MD, PhD, chair of the University of Pittsburgh Department of Physical Medicine and Rehabilitation – along with experts from Pitt’s departments of surgery and orthopaedics and trauma and the Pittsburgh Trauma Research Center – published a study titled "Role of Autophagy in Intervertebral Disc Degeneration" in early 2022.

Intervertebral disc degeneration (IDD) is a leading contributor to low back pain. The intervertebral disc (IVD) is composed of three tissue types: the central gelatinous nucleus pulposus (NP) tissue, the surrounding annulus fibrosus (AF) tissue, and the inferior and superior cartilage endplates. The IVD microenvironment is hypoxic, acidic, hyperosmotic, and low in nutrients because it is mostly avascular. 

The cellular processes that underlie IDD initiation and progression are still poorly understood. Specifically, a lack of understanding regarding NP cell metabolism and physiology hinders the development of effective therapeutics to treat IDD patients.

Autophagy is a vital intracellular degradation process that removes damaged organelles, misfolded proteins, and intracellular pathogens and recycles the degraded components for cellular energy and function. NP cells have adapted to survive within their harsh tissue microenvironment using processes that are largely unknown, and the research team postulates autophagy is one of these undiscovered mechanisms.

In this review, the team describes unique features of the IVD tissue, reviews how physiological stressors impact autophagy in NP cells in vitro, surveys the current understanding of autophagy regulation in the IVD, and assesses the relationship between autophagy and IDD.

Published studies confirm autophagy markers are present in IVD tissue, and IVD cells can regulate autophagy in response to cellular stressors in vitro. However, data are still lacking to determine the exact mechanisms regulating autophagy in IVD cells. More in-depth research is needed to establish whether autophagy is necessary to maintain IVD cell health and validate autophagy as a relevant therapeutic target for treating IDD.

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