Unravelling the glycome in human intervertebral disc degeneration: Aberrant glycosylation modulates inflammation and metabolism.

Intervertebral disc (IVD) degeneration is one of the major contributing causes of low back pain (LBP), a common health issue that imposes a significant socio-economic burden on society. Previous work has demonstrated a dysregulated glycome in animal models of IVD degeneration; however, the role of glycosylation in pathogenesis is unknown. The objective of this study was to characterise altered glycan expression in IVD degeneration and elucidate the functional role of this response. Glycans in human healthy and degenerated IVD (n=6) were examined through UPLC-MS and MALDI-IMS. These findings were correlated with proteomic analysis by LC-MS and functional in vitro studies using RNA sequencing. IVD degeneration was associated with a hypersialylated N-glycome, predominantly α-2,6 linked sialic acid. Confirming hypersialylation, we investigated sialylation's functional role through mechanistic studies using a sialylation inhibitor (3Fax-peracetyl Neu5Ac). Sialylation inhibition in vitro modulated inflammatory and metabolic pathways, demonstrating a functional role for glycosylation in IVD degeneration.