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08.06.2023 | RESEARCH

Glipizide Alleviates Periodontitis Pathogenicity via Inhibition of Angiogenesis, Osteoclastogenesis and M1/M2 Macrophage Ratio in Periodontal Tissue

verfasst von: Xueqi Guo, Zhijun Huang, Qing Ge, Luxi Yang, Dongliang Liang, Yinyin Huang, Yiqin Jiang, Janak Lal. Pathak, Lijing Wang, Linhu Ge

Erschienen in: Inflammation | Ausgabe 5/2023

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Abstract

New consensus indicates type 2 diabetes mellitus (T2DM) and periodontitis as comorbidity and may share common pathways of disease progression. Sulfonylureas have been reported to improve the periodontal status in periodontitis patients. Glipizide, a sulfonylurea widely used in the treatment of T2DM, has also been reported to inhibit inflammation and angiogenesis. The effect of glipizide on the pathogenicity of periodontitis, however, has not been studied. We developed ligature-induced periodontitis in mice and treated them with different concentrations of glipizide and then analyzed the level of periodontal tissue inflammation, alveolar bone resorption, and osteoclast differentiation. Inflammatory cell infiltration and angiogenesis were analyzed using immunohistochemistry, RT-qPCR, and ELISA. Transwell assay and Western bolt analyzed macrophage migration and polarization. 16S rRNA sequencing analyzed the effect of glipizide on the oral microbial flora. mRNA sequencing of bone marrow-derived macrophages (BMMs) stimulated by P. gingivalis lipopolysaccharide (Pg-LPS) after treatment with glipizide was analyzed. Glipizide decreases alveolar bone resorption, periodontal tissue degradation, and the number of osteoclasts in periodontal tissue affected by periodontitis (PAPT). Glipizide-treated periodontitis mice showed reduced micro-vessel density and leukocyte/macrophage infiltration in PAPT. Glipizide significantly inhibited osteoclast differentiation in vitro experiments. Glipizide treatment did not affect the oral microbiome of periodontitis mice. mRNA sequencing and KEGG analysis showed that glipizide activated PI3K/AKT signaling in LPS-stimulated BMMs. Glipizide inhibited the LPS-induced migration of BMMs but promoted M2/M1 macrophage ratio in LPS-induced BMMs via activation of PI3K/AKT signaling. In conclusion, glipizide inhibits angiogenesis, macrophage inflammatory phenotype, and osteoclastogenesis to alleviate periodontitis pathogenicity suggesting its’ possible application in the treatment of periodontitis and diabetes comorbidity.

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Titel: Glipizide Alleviates Periodontitis Pathogenicity via Inhibition of Angiogenesis, Osteoclastogenesis and M1/M2 Macrophage Ratio in Periodontal Tissue
verfasst von: Xueqi Guo
Zhijun Huang
Qing Ge
Luxi Yang
Dongliang Liang
Yinyin Huang
Yiqin Jiang
Janak Lal. Pathak
Lijing Wang
Linhu Ge
Publikationsdatum: 08.06.2023
Verlag: Springer US
Erschienen in: Inflammation / Ausgabe 5/2023
Print ISSN: 0360-3997
Elektronische ISSN: 1573-2576
DOI: https://doi.org/10.1007/s10753-023-01850-1

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