# Inhibition of Hypersialylation in Human Intervertebral Disc Degeneration Modulates Inflammation and Metabolism

## TL;DR

This study finds that hypersialylation in degenerating spinal discs contributes to inflammation and suggests that targeting this process could lead to new treatments.

## Contribution

The study identifies hypersialylation as a novel driver of intervertebral disc degeneration and shows its inhibition reduces inflammation and oxidative stress.

## Key findings

- Hypersialylation, especially α-2,6-linked sialic acid, is a prominent feature in degenerated intervertebral discs.
- Inhibiting sialylation in nucleus pulposus cells reduces oxidative stress and inflammatory signaling.
- Targeting glycosylation pathways, particularly sialylation, is proposed as a promising therapeutic strategy for disc degeneration.

## Abstract

Intervertebral disc (IVD) degeneration is a major cause of low back pain (LBP), a significant global health burden. While glycosylation plays a key role in cellular signaling and inflammation, its role in IVD degeneration remains poorly understood. This study characterizes glycan alterations in human healthy and degenerated IVDs using glycomic (UPLC‐MS, MALDI‐IMS) and proteomic (LC‐MS) analyses, combined with functional studies. These results identify hypersialylation, especially α‐2,6‐linked sialic acid, as a prominent feature of degenerated IVDs. In vitro inhibition of sialylation (3Fax‐peracetyl Neu5Ac) in nucleus pulposus cells demonstrates reduced oxidative stress and inflammatory signaling, indicating a functional role for hypersialylation in IVD pathology. Targeting glycosylation pathways, notably sialylation, emerges as a promising therapeutic strategy for IVD degeneration.

Glycosylation, specifically hypersialylation, is identified as a critical factor in human intervertebral disc (IVD) degeneration—a major cause of low back pain. This study demonstrates that inhibiting sialylation reduces inflammation and oxidative stress in IVD tissues, suggesting new therapeutic possibilities. These findings highlight glycan modifications as promising targets for improving outcomes in degenerative disc diseases.