In vitro and in vivo study of the pathogenic role of PPARα in experimental periodontitis

Abstract

Objective The purpose of this study is to investigate the pathogenic role of PPARα in periodontal antigen treated gingival cells in vitro and in experimental periodontitis in vivo . Methodology Gingival fibroblasts, gingival epithelial cells and splenocytes were isolated from C57BL/6J wild type (WT) mice and treated with fixed P. gingivalis at for 48 hours. The mRNA levels of PPARs, TNFα, IL-1β and IL-10 were detected by Real-time quantitative PCR. Silk ligatures after being soaked in the P.gingivalis suspension were tied around both maxillary second molars of WT mice or PPARα knock-out (KO) mice for two weeks. PPARα agonist fenofibrate and vehicle control were injected into the different side of the palatal gingiva on days 3, 6, and 9. At day 14, bone resorption and gingival mRNA expression levels of PPARs, TNFα, IL-1β and IL-10 were measured by micro-computed tomography and RT-qPCR respectively. Results P. gingivalis treatment downregulated the expression of PPARα, but not PPARβ or PPARγ, and increased the expression of TNF-α and IL-1β in Gingival fibroblasts, gingival epithelial cells and splenocytes from WT mice. Gingival mRNA levels of PPARα were significantly decreased in experimental periodontitis in WT mice. The bone loss of PPARα KO mice in experimental periodontitis was significantly higher than WT mice and was not reduced by fenofibrate treatment. Gingival TNFα protein expressions were significantly increased by P. gingivalis associated ligation and decreased by fenofibrate treatment in WT mice but not in PPARα KO mice. Conclusion This study suggests that PPARα plays an essential role in periodontitis.

Genetic Analysis of Exacerbated Healing Responses after Periodontal Therapy due to Type 2 Diabetes: Clinical and in vivo Studies

“…Recently, PPAR signaling has been reported to be protective against progression of periodontitis 39 . In ligature models, PPARα expression in the gingiva was decreased 40 and bone loss was signi cantly greater in PPARα knockout mice than that in wild-type mice, suggesting that decreased PPARα expression associates with the increased bone resorption 40 . In another in vivo study with a rodent ligature model, treatment with the PPARα agonist WY14643 reduced the in ammatory markers 37 .…”

Wnt Signaling Activation in Gingival Epithelial Cells and Macrophages of Experimental Periodontitis

“…Cell preparation and culture: Mouse gingival epithelial cells were isolated and cultured following a procedure described previously [20]. Briefly, the palatal gingival tissue was minced by scalpel and then put in solutions containing Dispase II (2 mg/mL, Sigma, St. Louis, MO, USA) and collagenase (4 mg/mL, Sigma) for 1.5 h at 37 • C. After centrifugation and rinsing, the cells were separated and cultured in keratinocyte serum-free medium (Gibco, Waltham, MA, USA) for 7 days, after which they were ready to use.…”

Genetic analysis of impaired healing responses after periodontal therapy in type 2 diabetes: Clinical and in vivo studies

“…51 Recently, PPAR signaling has been reported to be protective against progression of periodontitis. 52 In EP models, PPARα expression in the gingiva was decreased 53 and bone loss was significantly greater in PPARα knockout mice than that in wild-type mice, suggesting that decreased PPARα expression associates with the increased bone resorption. 53 In another in vivo study with a rodent EP model, treatment with the PPARα agonist WY14643 reduced the inflammatory markers.…”

“…52 In EP models, PPARα expression in the gingiva was decreased 53 and bone loss was significantly greater in PPARα knockout mice than that in wild-type mice, suggesting that decreased PPARα expression associates with the increased bone resorption. 53 In another in vivo study with a rodent EP model, treatment with the PPARα agonist WY14643 reduced the inflammatory markers. 49 Systemic administration of GW0742, a PPARβ/δ agonist, suppressed EP and tissue damage.…”