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

Abstract

BackgroundDiabetes 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 designA 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. ResultsWe 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. ConclusionDiabetic 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.