There is a strong association between vitamin D levels and periodontal disease based on numerous epidemiological studies. We have previously shown that experimental deficiency of serum vitamin D in mice leads to gingival inflammation and alveolar bone loss. Treatment of cultured oral epithelial cells with the active form of vitamin D, 1,25(OH)2 vitamin D3 (1,25(OH)2D3), inhibits the extracellular growth and intracellular invasion of bacteria associated with periodontal disease. Maintenance of periodontal health may be due in part to the anti-inflammatory activities of vitamin D. Furthermore, this hormone can induce the expression of an antimicrobial peptide in cultured oral epithelial cells. We have shown that oral epithelial cells are capable of converting inactive vitamin D to the active form, suggesting that topical treatment of the oral epithelium with inactive vitamin D could prevent the development of periodontitis. We subjected mice to ligature-induced periodontitis (LIP), followed by daily treatment with inactive vitamin D or 1,25(OH)2D3. Treatment with both forms led to a reduction in ligature-induced bone loss and inflammation. Gingival tissues obtained from vitamin D–treated LIP showed production of specialized proresolving mediators (SPM) of inflammation. To examine the mechanism, we demonstrated that apical treatment of 3-dimensional cultures of primary gingival epithelial cells with vitamin D prevented lipopolysaccharide-induced secretion of proinflammatory cytokines and led to a similar production of SPM. Analysis of the oral microbiome of the mice treated with vitamin D showed significant changes in resident bacteria, which reflects a shift toward health-associated species. Together, our results show that topical treatment of oral tissues with inactive vitamin D can lead to the maintenance of periodontal health through the regulation of a healthy microbiome and the stimulation of resolution of inflammation. This strongly supports the development of a safe and effective vitamin D–based topical treatment or preventive agent for periodontal inflammation and disease.

中文翻译：

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外用维生素 D 可防止小鼠模型中的骨质流失和炎症


根据大量流行病学研究，维生素 D 水平与牙周病之间存在很强的相关性。我们之前已经表明，小鼠血清维生素 D 的实验性缺乏会导致牙龈炎症和牙槽骨流失。用维生素 D 的活性形式 1,25（OH）2 维生素 D3 （1,25（OH）2D3） 处理培养的口腔上皮细胞，抑制与牙周病相关的细菌的细胞外生长和细胞内侵袭。维持牙周健康可能部分归因于维生素 D 的抗炎活性。此外，这种激素可以在培养的口腔上皮细胞中诱导抗菌肽的表达。我们已经表明，口腔上皮细胞能够将非活性维生素 D 转化为活性形式，这表明用非活性维生素 D 局部治疗口腔上皮可以预防牙周炎的发展。我们让小鼠接受结扎诱导的牙周炎 （LIP），然后每天用非活性维生素 D 或 1,25（OH）2D3 治疗。两种形式的治疗都减少了结扎诱导的骨质流失和炎症。从维生素 D 处理的 LIP 获得的牙龈组织显示炎症的专门促消退介质 （SPM） 的产生。为了检查机制，我们证明用维生素 D 对原代牙龈上皮细胞的 3 维培养物进行顶端处理可防止脂多糖诱导的促炎细胞因子分泌，并导致类似的 SPM 产生。对用维生素 D 治疗的小鼠的口腔微生物组的分析显示，驻留细菌发生了显着变化，这反映了向健康相关物种的转变。 总之，我们的结果表明，用非活性维生素 D 对口腔组织进行局部治疗可以通过调节健康的微生物组和刺激炎症消退来维持牙周健康。这有力地支持开发一种安全有效的基于维生素 D 的局部治疗或预防剂，用于治疗牙周炎和疾病。