Hyperbaric oxygen protects against periodontal bone loss by modulating inflammation and bone remodeling via RANKL/OPG expression in ligature-induced periodontitis

TL;DR

Hyperbaric oxygen therapy reduces periodontal bone loss by decreasing inflammation and balancing bone remodeling in a rat model of periodontitis.

Contribution

This study demonstrates that early hyperbaric oxygen therapy effectively modulates RANKL/OPG expression and inflammatory pathways to prevent periodontal bone loss.

Findings

Early HBOT significantly reduced bacterial metabolites and pro-inflammatory mediators compared to late HBOT or natural recovery.

HBOT restored the RANKL/OPG balance in osteoblasts and osteocytes, suppressing osteoclastogenesis.

Histological and micro-CT analyses confirmed HBOT's ability to preserve trabecular bone microarchitecture.

Abstract

Periodontitis (PD) is a chronic inflammatory disease characterized by the accumulation of bacterial metabolites, sustained immune activation, and progressive loss of alveolar bone. Hyperbaric oxygen therapy (HBOT) has demonstrated anti-inflammatory and bone-reparative properties; however, its mechanistic effects in periodontitis remain underexplored. This study investigated whether HBOT mitigates periodontal bone loss and modulates bacterial, inflammatory, and osteoclastogenic pathways in a ligature-induced rat model. Sixty male Wistar rats underwent ligature placement for 28 days and were allocated into five groups (Sham, PD, PD+ natural recovery [RECOV], PD+early HBOT [EHBOT], PD+late HBOT [LHBOT]); HBOT was delivered as 100% oxygen at 2.0 ATA for 60 min/day. Gingival tissues were assessed for bacterial metabolites, lipoteichoic acid (LTA) and lipopolysaccharide (LPS), inflammatory cell infiltration, fibrotic integrity, and alveolar bone resorption. Cytokine and chemokine arrays were performed to evaluate cytokine-induced neutrophil chemoattractants, interleukin-1α, interleukin-1β, interleukin-1 receptor antagonist, LPS-induced chemokine CXCL5, thymus chemokine, tissue inhibitor of metalloproteinases-1, soluble intercellular adhesion molecule-1, and L-selectin. Ligature-induced periodontitis triggered robust inflammatory responses, elevated bacterial burden, increased receptor activator of nuclear factor kappa-B ligand (RANKL), and suppressed osteoprotegerin (OPG), promoting osteoclastogenesis and bone loss. Importantly, EHBOT produced more pronounced reductions in LTA/LPS and pro-inflammatory mediators and yielded greater preservation of trabecular microarchitecture than LHBOT or RECOV. HBOT overall significantly reduced LTA/LPS levels, suppressed inflammatory cytokines and adhesion molecules, and restored the RANKL/OPG balance in osteoblasts and osteocytes. Histological and micro-computed tomography analyses confirmed that HBOT preserved trabecular bone microarchitecture. These findings highlight the multi-targeted therapeutic potential of HBOT in suppressing inflammation, limiting immune cell infiltration, and preventing bone destruction, supporting its use as an adjunctive intervention for periodontitis and inflammatory bone disorders.

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