K L Kirkwood, T E Van Dyke, C L Kirkwood, L Zhang, J Panezai, A E Duran-Pinedo, E L Figgins, L K Ryan, J J Frias-Lopez, G Diamond
{"title":"Topical Vitamin D Prevents Bone Loss and Inflammation in a Mouse Model.","authors":"K L Kirkwood, T E Van Dyke, C L Kirkwood, L Zhang, J Panezai, A E Duran-Pinedo, E L Figgins, L K Ryan, J J Frias-Lopez, G Diamond","doi":"10.1177/00220345241259417","DOIUrl":null,"url":null,"abstract":"<p><p>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)<sub>2</sub> vitamin D<sub>3</sub> (1,25(OH)<sub>2</sub>D<sub>3</sub>), 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)<sub>2</sub>D<sub>3</sub>. 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.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"908-915"},"PeriodicalIF":0.0000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11465324/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of dental research","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1177/00220345241259417","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/8/5 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
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.
根据大量流行病学研究,维生素 D 水平与牙周病之间存在密切联系。我们以前的研究表明,小鼠实验性血清维生素 D 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,可抑制与牙周病相关的细菌的胞外生长和胞内侵袭。此外,这种激素还能诱导培养的口腔上皮细胞表达一种抗菌肽。我们已经证明,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 局部治疗口腔上皮细胞可以预防牙周炎的发生。我们对小鼠进行了结扎诱导的牙周炎(LIP)治疗,然后每天用非活性维生素 D 或 1,25(OH)2D3进行治疗。这两种维生素都能减少结扎诱发的骨质流失和炎症。从经维生素 D 处理的 LIP 中获得的牙龈组织显示,产生了专门的炎症促溶解介质(SPM)。为了研究其机理,我们证明了用维生素 D 对原代牙龈上皮细胞的三维培养物进行根尖处理可防止脂多糖诱导的促炎细胞因子的分泌,并导致产生类似的 SPM。对接受维生素 D 治疗的小鼠口腔微生物组的分析表明,常驻细菌发生了显著变化,这反映出小鼠口腔微生物组向与健康相关的菌种转变。总之,我们的研究结果表明,用非活性维生素 D 局部治疗口腔组织可通过调节健康的微生物群和刺激炎症消退来维持牙周健康。这有力地支持了以安全有效的维生素 D 为基础的牙周炎症和疾病局部治疗或预防剂的开发。