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

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.