Roles of large aggregating proteoglycans in human intervertebral disc degeneration

ABSTRACT

Degeneration of the intervertebral discs, a natural progression of the aging process, is strongly implicated as a cause of low back pain. Aggrecan is the major structural proteoglycan in the extracellular matrix of the intervertebral disc. It is large, possessing numerous glycosaminoglycan chains and the ability to form aggregates in association with hyaluronan. The negatively charged glycosaminoglycan side chains in aggrecan in the nucleus pulposus of the intervertebral discs can bind electrostatically to polar water molecules, which are crucial for maintaining the well-hydrated state that enables the discs to undergo reversible deformation under compressive loading. A more in-depth understanding of the molecular basis of disc degeneration is essential to the design of therapeutic solutions to treat degenerative discs. Within this scope, we discuss the current knowledge concerning the structure and function of aggrecan in intervertebral disc degeneration. These data suggest that aggrecan plays a central role in the function and degeneration of the intervertebral disc, which may suggest potential aggrecan-based therapies for disc regeneration.

KEYWORDS:

• Aggrecan
• degeneration
• glycosaminoglycans
• intervertebral discs
• low back pain
• proteoglycans

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [grant number 81772920].