Department of Oral Biology, University at Buffalo, Buffalo, New York, USA.
Department of Applied Oral Sciences, The Forsyth Institute, Cambridge, MA, USA.
J Dent Res. 2024 Aug;103(9):908-915. doi: 10.1177/00220345241259417. Epub 2024 Aug 5.
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) vitamin D (1,25(OH)D), 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)D. 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.
基于大量的流行病学研究，维生素 D 水平与牙周病之间存在很强的关联。我们之前已经表明，实验性缺乏血清维生素 D 会导致牙龈炎症和牙槽骨丢失。用维生素 D 的活性形式 1,25-二羟维生素 D（1,25(OH)D）处理培养的口腔上皮细胞可抑制与牙周病相关的细菌的细胞外生长和细胞内入侵。牙周健康的维持部分可能归因于维生素 D 的抗炎活性。此外，这种激素可以诱导培养的口腔上皮细胞中表达一种抗菌肽。我们已经表明，口腔上皮细胞能够将无活性的维生素 D 转化为活性形式，这表明用无活性的维生素 D 对口腔上皮进行局部治疗可能预防牙周炎的发生。我们使小鼠发生结扎诱导的牙周炎（LIP），然后每天用无活性的维生素 D 或 1,25(OH)D 治疗。两种形式的治疗均导致结扎诱导的骨丢失和炎症减少。用维生素 D 治疗的 LIP 牙龈组织显示出炎症的特殊促解决介质（SPM）的产生。为了研究机制，我们证明了用维生素 D 对原发性牙龈上皮细胞的三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的分泌，并导致类似的 SPM 产生。用维生素 D 处理的小鼠的口腔微生物组分析显示常驻细菌发生了显著变化，这反映了向健康相关物种的转变。总之，我们的研究结果表明，用无活性的维生素 D 对口腔组织进行局部治疗可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。这强烈支持开发安全有效的基于维生素 D 的局部治疗或预防牙周炎和疾病的药物。
