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

Background: Diabetes is a known age-related disease. Inflammaging has recently been shown to result in diabetic complications. Vitamin D-3 is related to aging in the latest study but little is known about the underlying mechanism. Here, we investigated the effects of 25-Hydroxyvitamin D-3 (25(OH)D-3) 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)D-3, periodontitis-db/db mice presented increased levels of serum 25(OH)D-3, 1 alpha,25-Dihydroxyvitamin D-3 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-kappa B and IL-1 beta, 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)D-3 could inhibit SASP secretion through reducing SOCS3 expression in experimental diabetic periodontitis, dependently inactivating NF-kappa B pro-inflammatory signaling. The reversible effect further documented that the inflammaging might be a highly likely contributor in diabetic periodontitis.