Intermittent parathyroid hormone (1-34) ameliorates periodontitis via Treg-dependent immunomodulation of the Treg/Th17 axis.

OBJECTIVES

The intermittent administration of parathyroid hormone 1-34 (iPTH) is a bone anabolic therapy with potential for periodontitis treatment, but its immunomodulatory mechanisms remain unclear. This study investigated whether iPTH ameliorates periodontitis by modulating the regulatory T cell (Treg)/T helper cell (Th17) balance.

METHODS

Experimental periodontitis was induced in mice by ligature. Mice were assigned to control, periodontitis, or iPTH-treated periodontitis groups. Alveolar bone loss was analyzed by micro computed tomography. Bone turnover, cytokines and immune cells were assessed by histology, immunohistochemistry, immunofluorescence, quantitative polymerase chain reaction, and flow cytometry. The role of Tregs was verified via anti-CD25 antibody-mediated depletion.

RESULTS

iPTH treatment significantly attenuated alveolar bone loss, improved trabecular microarchitecture, enhanced osteoblast activity, and suppressed osteoclastogenesis. Besides, iPTH suppressed the inflammatory level, downregulating interleukin (IL)-6, IL-17a, receptor activator of nuclear factor-κB ligand (RANKL), while upregulating IL-10. Crucially, iPTH shifted the Treg/Th17 functional axis toward an anti-inflammatory state, increasing Treg proportions in cervical lymph nodes and forkhead box protein P3 (FOXP3) level while simultaneously suppressing IL-17 in gingiva. Furthermore, iPTH reduced the periodontitis-enhanced spatial proximity between FOXP3 and IL-17. Depletion of Tregs impaired the bone-protective effects of iPTH.

CONCLUSIONS

iPTH ameliorates periodontitis-induced alveolar bone loss through a Treg-dependent mechanism. This identifies the immunomodulation of the Treg/Th17 axis as a pivotal mechanism underlying iPTH's efficacy, highlighting its potential as a host-modulating therapy for periodontitis.