Effect of 1,25(OH)2 D3 and 20(OH)D3 on interleukin-1ß-stimulated interleukin-6 and -8 production by human gingival fibroblasts.

BACKGROUND AND OBJECTIVE: Vitamin D-1,25(OH)2 D3 or 1,25D3-maintains healthy osseous tissue, stimulates the production of the antimicrobial peptide cathelicidin and has anti-inflammatory effects, but it can cause hypercalcemia. Evidence links diminished serum levels of 1,25D3 with increased gingival inflammation. Periodontitis progression is associated with increased local production of inflammatory mediators by immune cells and gingival fibroblasts. These include interleukin (IL)-6, a regulator of osteoclastic bone resorption, and the neutrophil chemoattractant IL-8, both regulated by signaling pathways, including NF-κB and MAPK/AP-1. The objectives were to determine the effects of 1,25D3 or a non-calcemic analog, 20-hydroxyvitamin D3 -20(OH)D3 or 20D3-on IL-1ß-stimulated IL-6 and IL-8 production, and NF-κB and MAPK/AP-1 activation, by human gingival fibroblasts. MATERIAL AND METHODS: Human gingival fibroblasts were incubated ± IL-1ß, with or without exposure to 1,25D3 or 20D3. IL-6 and IL-8 in culture supernatants were measured by enzyme-linked immunosorbent assay. NF-κB (p65) and AP-1 (phospho-cJun) and were measured in nuclear extracts via binding to specific oligonucleotides. Data were analyzed using ANOVA and Scheffe's F procedure for post hoc comparisons. RESULTS: IL-1ß-stimulated IL-6 and IL-8 levels were both significantly inhibited (40%-60%) (P<.045) by 1,25D3, but not 20D3 (0%-15% inhibition, not statistically significant). Both 1,25D3 and 20D3 significantly and similarly inhibited IL-1ß-stimulated nuclear levels of p65 and phospho-cJun (P<.02). CONCLUSION: Reduction of the activation of NF-κB and AP-1 alone is not able to inhibit strongly the IL-1ß stimulated IL-6 and IL-8 gene expression. 1,25D3 but not 20D3 may affect some of the many other factors/processes/pathways that in turn regulate the expression of these genes. However, the results suggest that topical application of ligands of the vitamin D receptor may be useful in the local treatment of periodontitis while reducing adverse systemic effects.

Re-evaluating the role of vitamin D in the periodontium.

The importance of vitamin D in maintaining skeletal health via the regulation of calcium has long been recognized as a critical function of this secosteroid. An abundance of literature shows an association between oral bone mineral density and some measure of systemic osteoporosis and suggests that osteoporosis/low bone mass may be a risk factor for periodontal disease. Recently, nonskeletal functions of vitamin D have gained notoriety for several reasons. Many cells that are not associated with calcium homeostasis have been demonstrated to possess membrane receptors for vitamin D. These include activated T and B lymphocytes, and skin, placenta, pancreas, prostate and colon cancer cells. In addition, vitamin D "insufficiency" is a worldwide epidemic and epidemiologic evidence has linked this condition to multiple chronic health problems, including cardiovascular and autoimmune diseases, hypertension and a variety of cancers. Interestingly, there is mounting evidence connecting diminished serum levels of vitamin D with increased gingival inflammation and supporting the concept of "continual vitamin D sufficiency" in maintaining periodontal health. The ability of vitamin D to regulate both the innate and the adaptive components of the host response may play an important role in this process. This review will examine the skeletal and nonskeletal functions of vitamin D, and explore its potential role in protecting the periodontium as well as in regulating periodontal wound healing.

Calcium channel blocker-induced gingival enlargement.

Despite the popularity and wide acceptance of the calcium channel blockers (CCBs) by the medical community, their oral impact is rarely recognized or discussed. CCBs, as a group, have been frequently implicated as an etiologic factor for a common oral condition seen among patients seeking dental care: drug-induced gingival enlargement or overgrowth. This enlargement can be localized or generalized, and can range from mild to extremely severe, affecting patient's appearance and function. Treatment options for these patients include cessation of the offending drug and substitution with another class of antihypertensive medication to prevent recurrence of the lesions. In addition, depending on the severity of the gingival overgrowth, nonsurgical and surgical periodontal therapy may be required. The overall objective of this article is to review the etiology and known risk factors of these lesions, their clinical manifestations and periodontal management.