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25‐Hydroxyvitamin D 3 ‐enhanced PTPN 2 positively regulates periodontal inflammation through the JAK / STAT pathway in human oral keratinocytes and a mouse model of type 2 diabetes mellitus
Author(s) -
Zhang P.,
Zhang W.,
Zhang D.,
Wang M.,
Aprecio R.,
Ji N.,
Mohamed O.,
Li Y.,
Ding Y.,
Wang Q.
Publication year - 2018
Publication title -
journal of periodontal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.31
H-Index - 83
eISSN - 1600-0765
pISSN - 0022-3484
DOI - 10.1111/jre.12535
Subject(s) - porphyromonas gingivalis , inflammation , periodontitis , endocrinology , immunology , signal transduction , medicine , cancer research , biology , microbiology and biotechnology
Background and Objective Periodontitis is an increasingly prevalent complication of diabetes mellitus (known as diabetes mellitus‐associated periodontitis), and 25‐hydroxyvitamin D 3 (25VD 3 ) was recently found to be a critical regulator of innate immunity in this disease, but the underlying mechanisms remain poorly understood. T‐cell protein tyrosine phosphatase non‐receptor type 2 ( PTPN 2) is a potential downstream protein of the 25 VD 3 /vitamin D receptor pathway. The aim of this study was to investigate the regulation of PTPN 2 in periodontal inflammation in diabetes mellitus‐associated periodontitis. Material and Methods Porphyromonas gingivalis ‐infected db/db mice were treated with 25 VD 3 . Their fasting blood glucose and body weight were monitored every other week, and the levels of alveolar bone loss and serum inflammatory cytokines (tumor necrosis factor‐α, interferon‐γ and interleukin‐6) were determined at the time of killing. The effect of PTPN 2 on human OKF 6‐ TERT 2 oral keratinocytes was examined through the knockout of PTPN 2 using the CRISPR /Cas9 knockout plasmid. The expression levels of the PTPN 2, vitamin D receptor and JAK 1/ STAT 3 signaling proteins in the gingival epithelium and OKF 6‐ TERT 2 cells were determined through western blot and immunohistochemical analyses. Results After 25 VD 3 treatment, db/db mice exhibited alleviated serum inflammatory cytokines and alveolar bone loss, and 25 VD 3 ‐enhanced PTPN 2 expression decreased the expression of the JAK 1/ STAT 3 signaling proteins in the gingival epithelium. Analyses of human oral keratinocytes showed that 25 VD 3 increased the expression of PTPN 2, which dephosphorylates protein substrates in the JAK 1/ STAT 3 signaling pathway. Conclusion PTPN 2 contributed to a decrease in periodontal inflammation in type 2 diabetes mellitus via dephosphorylate protein substrates in the JAK 1/ STAT 3 signaling pathway after 25 VD 3 treatment in human oral keratinocytes and a mouse model of type 2 diabetes mellitus. A thorough understanding of PTPN 2 and its involvement in inhibiting inflammation might provide alternative therapeutic approaches for the pathogenesis and treatment of diabetes mellitus‐associated periodontitis.