Regulation of NAMPT in Human Gingival Fibroblasts and Biopsies

Abstract

Adipokines, such as nicotinamide phosphoribosyltransferase (NAMPT), are molecules, which are produced in adipose tissue. Recent studies suggest that NAMPT might also be produced in the tooth-supporting tissues, that is, periodontium, which also includes the gingiva. The aim of this study was to examine if and under what conditions NAMPT is produced in gingival fibroblasts and biopsies from healthy and inflamed gingiva. Gingival fibroblasts produced constitutively NAMPT, and this synthesis was significantly increased by interleukin-1β and the oral bacteria P. gingivalis and F. nucleatum. Inhibition of the MEK1/2 and NFκB pathways abrogated the stimulatory effects of F. nucleatum on NAMPT. Furthermore, the expression and protein levels of NAMPT were significantly enhanced in gingival biopsies from patients with periodontitis, a chronic inflammatory infectious disease of the periodontium, as compared to gingiva from periodontally healthy individuals. In summary, the present study provides original evidence that gingival fibroblasts produce NAMPT and that this synthesis is increased under inflammatory and infectious conditions. Local synthesis of NAMPT in the inflamed gingiva may contribute to the enhanced gingival and serum levels of NAMPT, as observed in periodontitis patients. Moreover, local production of NAMPT by gingival fibroblasts may represent a possible mechanism whereby periodontitis may impact on systemic diseases.

Beneficial Effects of Adiponectin on Periodontal Ligament Cells under Normal and Regenerative Conditions

“…Moreover, periodontopathogens, such as P. gingivalis , were capable of inhibiting the adiponectin expression and stimulating the expression of its receptors. These novel observations are in accordance with our previous study, which has demonstrated a downregulation of adiponectin and an upregulation of its receptors in gingival biopsies from periodontally diseased subjects as compared to periodontally healthy individuals [48]. Our findings also concur with the clinical observations that plasma adiponectin levels are decreased in periodontitis and increased again after periodontal therapy [47, 73–75].…”

“…As in our previous studies, cells were exposed to IL-1 β , which was used to mimic inflammatory conditions in vitro [43, 46, 48, 50]. This proinflammatory cytokine is increased in GCF and gingival tissues at inflamed sites [76–78].…”

Expression of Leptin and Visfatin in Gingival Tissues of Chronic Periodontitis With and Without Type 2 Diabetes Mellitus: A Study Using Enzyme‐Linked Immunosorbent Assay and Real‐Time Polymerase Chain Reaction

“…Interestingly, an in vitro study 40 demonstrated that periodontopathogenic bacteria and inflammatory stimuli caused a significant downregulation of leptin and its receptor in periodontal ligament cells, which might explain, at least in part, the reduced GCF leptin levels found in periodontally diseased sites by other clinical studies. Furthermore, enhanced expression and protein levels of visfatin were found in gingival biopsies from sites of periodontitis compared with periodontally healthy gingiva, and this production was increased under infectious and inflammatory conditions 41 . According to those authors, the local production of visfatin by periodontal ligament cells and gingival fibroblasts may contribute to the enhanced gingival levels of visfatin observed in patients with periodontitis and may represent a possible pathomechanism whereby periodontal infections may have an impact on systemic diseases such as T2DM.…”

Non‐Surgical Periodontal Therapy Reduces Saliva Adipokine and Matrix Metalloproteinase Levels in Periodontitis

“…In this study, it was found that saliva visfatin levels were higher in patients with periodontitis than in the healthy individuals, which decreased at 3 months and remained low until 6 months. In several studies, high levels of visfatin have been reported in saliva, GCF, and periodontal tissue in periodontitis 6,7,41‐43 . In contrast, visfatin GCF and saliva levels have been reported to decrease after NSPT 15–18 .…”