Department of Conservative Dentistry and Periodontology, University Clinic of Dentistry, Medical University of Vienna, Vienna, Austria.
J Periodontol. 2021 Jan;92(1):137-148. doi: 10.1002/JPER.19-0541. Epub 2020 Jun 21.
Although vitamin D deficiency is considered as a risk factor for periodontitis, supplementation during periodontal treatment has not been shown to be beneficial to date. Human periodontal ligament cells (hPDLCs) are regulated by vitamin D and play a fundamental role in periodontal tissue homeostasis and inflammatory response in periodontitis. The aim of this study is to investigate possible alterations of the vitamin D activity in hPDLCs under inflammatory conditions.
Cells isolated from six different donors were treated with either 1,25(OH) D (0 to 10 nM) or 25(OH)D (0 to 100 nM) in the presence and absence of ultrapure or standard Porphyromonas gingivalis lipopolysaccharide (PgLPS), Pam3CSK4, or interferon-γ for 48 hours. Additionally, nuclear factor (NF)-κB inhibition was performed with BAY 11-7082. The bioactivity of vitamin D in hPDLCs was assessed based on the gene expression levels of vitamin D receptor (VDR)-regulated genes osteocalcin and osteopontin. Additionally, VDR and CYP27B1 expression levels were measured.
The vitamin D -induced increase of osteocalcin and osteopontin expression was significantly decreased in the presence of standard PgLPS and Pam3CSK4, which was not observed by ultrapure PgLPS. Interferon-y had diverse effects on the response of hPDLCs to vitamin D metabolites. NF-kB inhibition abolished the effects of standard PgLPS and Pam3CSK4. Standard PgLPS and Pam3CSK4 increased VDR expression in the presence of vitamin D . CYP27B1 expression was not affected by vitamin D and inflammatory conditions.
This study indicates that the transcriptional activity of VDR is diminished under inflammatory conditions, which might mitigate the effectiveness of vitamin D supplementation during periodontal treatment.
尽管维生素 D 缺乏被认为是牙周炎的一个危险因素，但迄今为止，在牙周病治疗中补充维生素 D 并没有显示出有益的效果。人牙周韧带细胞（hPDLCs）受维生素 D 调节，在牙周组织稳态和牙周炎的炎症反应中发挥着基本作用。本研究旨在探讨在炎症条件下 hPDLCs 中维生素 D 活性可能发生的变化。
从六位不同供体分离的细胞分别用 1,25(OH)D（0 到 10nM）或 25(OH)D（0 到 100nM）处理，同时存在或不存在超纯或标准牙龈卟啉单胞菌脂多糖（PgLPS）、Pam3CSK4 或干扰素-γ，处理时间为 48 小时。此外，还使用 BAY 11-7082 进行核因子（NF）-κB 抑制。根据维生素 D 受体（VDR）调节基因骨钙素和骨桥蛋白的基因表达水平来评估 hPDLCs 中维生素 D 的生物活性。此外，还测量了 VDR 和 CYP27B1 的表达水平。
在存在标准 PgLPS 和 Pam3CSK4 的情况下，维生素 D 诱导的骨钙素和骨桥蛋白表达增加显著降低，而在存在超纯 PgLPS 的情况下则没有观察到这种情况。干扰素-γ对 hPDLCs 对维生素 D 代谢物的反应有不同的影响。NF-kB 抑制消除了标准 PgLPS 和 Pam3CSK4 的作用。标准 PgLPS 和 Pam3CSK4 在存在维生素 D 的情况下增加了 VDR 的表达。CYP27B1 的表达不受维生素 D 和炎症条件的影响。
本研究表明，在炎症条件下，VDR 的转录活性降低，这可能会降低牙周病治疗期间补充维生素 D 的效果。
