Expression Levels of Adiponectin Receptors and the Etiology of Periodontitis

Objectives: We have recently shown that adiponectin, an adipocyte-derived cytokine, may negatively regulate the Toll-like receptor-signaling pathway and osteoclast formation in periodontal disease. In this study, we investigated whether the expression levels of adiponectin receptors (AdipoR1 and AdipoR2) are related to the etiology of periodotitis.

Methods: We firstly examined the expression of the AdipoR1 and AdipoR2 genes at the mRNA level in several oral tissues of C57/BL mouse using RT-PCR. Next, we investigated whether the inflammatory cytokine such as TNF-alpha could affect the expression levels of these adiponectin receptors in human normal gingival fibroblasts by real-time PCR assay using TaqMan probes. Lastly, we compared the expression levels of these receptors in gingival tissues between 2 healthy subjects and 4 patients of severe periodontal disease (50-55–year-old women) by Western blotting analysis. We ruled out obese and/or type 2 diabetes patients as subjects of this study. The Ethics Committee of Kyushu University Faculty of Dental Science approved this study and informed consent was obtained from all the patients before inclusion in the study.

Results: Both AdipoR1 and AdipoR2 receptors were ubiquitously found to be expressed in the mouse oral tissues. We next observed that TNF-alpha treatment (for 0.5 to 1 h) reduced the expression levels of the genes for both AdipoR1 and AdipoR2 in human gingival fibroblasts (P < 0.001). Moreover, Western blotting analysis showed that the expression of both receptors was remarkably decreased in periodontal tissues of severe periodontitis patients compared with those of healthy subjects.

Conclusion: These observations suggest that adiponectin cannot efficiently exhibit an anti-inflammatory effect in the periodontal site of patients, due to the decrease in the expression levels of adiponectin receptors. This adiponectin resistance may play a role in worsening periodontitis in patients.