25-Hydroxyvitamin D3 positively regulates periodontal inflammaging via SOCS3/STAT signaling in diabetic mice

Abstract

Background: Diabetes is a known age-related disease. Inflammaging has recently been shown to result in diabetic complications. Vitamin D₃ is related to aging in the latest study but little is known about the underlying mechanism. Here, we investigated the effects of 25-Hydroxyvitamin D₃ (25(OH)D₃) on inflammaging in diabetic periodontitis, a common chronic inflammatory diabetic complication.

Experimental design: A model of Porphyromonas gingivalis-infected db/db mice as experimental type 2 diabetic periodontitis was adopted in the whole study. A range of techniques, including microCT, western blotting, ELISA, histological and immunohistochemical analysis, were carried out in this study. The distinctive senescence-associated secretory phenotype (SASP) in serum was measured by Luminex technology.

Results: We found an archetypal inflammaging status occurred in db/db mice. An increased SASP, senescent enhancement, and periodontal destruction were observed in periodontitis-db/db mice. Upon administration with 25(OH)D₃, periodontitis-db/db mice presented increased levels of serum 25(OH)D₃, 1α,25-Dihydroxyvitamin D₃ and calcium. Moreover, decreased p16/p21-positive cells, relieved periodontal conditions and ameliorated serum SASP secretion were found in the periodontitis-db/db mice after treatment. Gingival tissue exhibited increased level of VDR and decreased expression of SOCS3, p-STAT3/STAT3, p-STAT5/STAT5, NF-κB and IL-1β, which were consistent with the change of p16/p21 expression.

Conclusion: Diabetic periodontitis appeared to develop an inflammaging status resulted in periodontal infection. 25(OH)D₃ could inhibit SASP secretion through reducing SOCS3 expression in experimental diabetic periodontitis, dependently inactivating NF-κB pro-inflammatory signaling. The reversible effect further documented that the inflammaging might be a highly likely contributor in diabetic periodontitis.

Keywords: 25-Hydroxyvitamin D(3); Diabetic periodontitis; Inflammaging; SOCS3; Senescence; Senescence-associated secretory phenotypes.