Fut8-Mediated Core Fucosylation of Toll-Like Receptor 4 Exacerbates Periodontitis Via Hyperactivation of NF-κB...

Chronic inflammation in periodontitis is linked to aberrant glycosylation, yet the molecular mechanisms and therapeutic potential of the core fucosyltransferase Fut8 remain undefined.

Gingival samples from healthy individuals and periodontitis patients were collected. Glycosylation levels were assessed using histological and molecular biological techniques. A mouse periodontitis model was established and injected with the core fucosylation inhibitor 2FF. Integrated transcriptomic and single-cell sequencing data were analysed to screen for key molecules. An in vitro human gingival fibroblast model was utilized. Gene silencing, coimmunoprecipitation, and pathway analysis were employed to elucidate the Fut8-Toll-like receptor 4 (TLR4) regulatory mechanism.

Core fucosylation levels were significantly elevated in periodontitis tissues. Inhibiting this modification alleviated gingival inflammation and bone resorption. Single-cell analysis identified fibroblasts as having the highest glycosylation activity, and Fut8 was pinpointed as the central regulatory molecule. Fut8 enhanced the sensitivity of the NF-κB pathway by mediating glycosylation of TLR4. Silencing Fut8 significantly suppressed inflammatory cytokine secretion. Dual-gene silencing confirmed that Fut8 and TLR4 synergistically drive the inflammatory cascade.

Fut8 amplifies NF-κB signalling through core fucosylation of TLR4. Targeted inhibition of Fut8 blocks periodontal tissue destruction, providing a theoretical basis for glycosylation-targeted therapy.

Targeting Fut8-mediated core fucosylation offers a promising therapeutic strategy to suppress inflammation and halt tissue destruction in periodontitis.