Local Sodium Tanshinone IIA Sulfonate Attenuates Periodontal Bone Loss by Modulating Inflammatory, Immune and Osteoclastogenic Signalling

Abstract

Aim

To investigate whether local administration of sodium tanshinone IIA sulfonate (STS) modulates periodontal inflammation, alveolar bone loss, immune response and bone remodelling–related signalling pathways in a ligature-induced murine model of periodontitis.

Materials and Methods

Sixty C57BL/6J male mice were randomly assigned to four groups: control group (C), periodontitis (P), low-dose (1 mg/kg) tanshinone (STS1) and high-dose (5 mg/kg) tanshinone treatment (STS5). Experimental periodontitis was induced by bilateral placement of ligatures around the first maxillary molars in the P, STS1 and STS5 groups. STS or vehicle was administered locally to the gingival tissues 2 days before disease induction and continued until the end of the experiment.

Results

STS significantly attenuated periodontal bone loss, preserved bone microarchitecture, reduced inflammatory infiltrate and maintained collagen organisation. Mechanistically, STS suppressed RANKL-dependent osteoclastogenesis by down-regulating RANKL, CTSK, MMP-9, OSCAR and NFATc1 mRNA expression while restoring the RANKL/OPG balance, thereby limiting osteoclast differentiation and activity. In parallel, STS attenuated inflammatory signalling by inhibiting NF-κB pathway activation, as reflected by reduced NF-κB protein levels, stabilisation of its inhibitory regulator IκBα as well as suppression of IL-6, TNF-α and TGF-β gene expression, followed by a trend towards reduced IFN-γ gene levels. STS further modulated macrophage polarisation by reducing M1-like macrophages, as shown by decreased F4/80⁺CD80⁺ signal, while CD206 immunoreactivity increased. At the protein level, STS reduced TRAP, CTSK and NFATc1 expression while restoring RUNX2.

Conclusion

STS effectively suppresses periodontal inflammation and alveolar bone destruction by modulating inflammatory signalling and attenuating M1-like macrophage polarisation, inhibiting osteoclastogenesis and partially restoring osteogenic pathways.