Therapeutic Potential of Liraglutide for Diabetes-Periodontitis Comorbidity: Killing Two Birds with One Stone.

Background: The relationship between diabetes and periodontitis is bidirectional, and there is now consensus that periodontitis and diabetes are comorbid. There is a quest for a drug that can be used to treat both conditions simultaneously. This study evaluated the anti-inflammatory and osteoprotective effects of liraglutide (LIRA) on periodontitis in diabetic rats. Methods: Male Wistar rats (n = 46) were randomly divided into four groups: control group (n = 8), LIRA group (n = 8), diabetes-associated periodontitis+0.9% saline group (diabetic periodontitis (DP)+NaCl group, n = 15), and diabetes-associated periodontitis+LIRA group (DP+LIRA group, n = 15). LIRA treatment lasted for 4 weeks (300 µg/kg/d) after establishment of a rat model of DP. The expression of IL-6, TNF-α, and IL-1ß was detected by enzyme-linked immunosorbent assay. The morphological changes of periodontal tissues were observed by hematoxylin-eosin staining. The absorption of alveolar bone and its ultrastructural changes were observed by histomorphometry and microcomputed tomography. The expression of receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) in alveolar bone was detected by immunohistochemistry. The levels of Runx2 mRNA and ALP mRNA in the gingival epithelium were examined by quantitative real-time polymerase chain reaction. Results: LIRA decreased alveolar bone resorption, improved the microstructure of alveolar bone, and reduced periodontal inflammation and damage (P < 0.05). LIRA also reduced blood glucose level and inhibited the secretion of serum IL-6, TNF-α, and IL-1ß (P < 0.05). In addition, after treatment with LIRA, the ratio of RANKL/OPG was reduced, and the expression levels of ALP mRNA and Runx2 mRNA were upregulated (P < 0.05). Conclusions: LIRA not only controls blood glucose level but also reduces inflammation and bone loss and enhances osteogenic differentiation in diabetes-associated periodontitis. Those indicate that LIRA may be used as a potential medicine for the adjunctive therapy of diabetes-periodontitis comorbidity.

Liraglutide regulates bone destruction and exhibits anti-inflammatory effects in periodontitis in vitro and in vivo.

OBJECTIVES: This study investigated the effect of Liraglutide (LIRA) on osteogenic differentiation of human periodontal ligament cells (hPDLCs) stimulated by Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) and its mechanismin in vitro. Further, investigated the osteoprotective and anti-inflammatory effects of LIRA in periodontitis in vivo. MATERIALS AND METHODS: ALP staining, Alizarin red staining(AR-S), qRT-PCR, Western Blot, and immunofluorescence staining were used to elucidate the effect of LIRA on osteogenesis of hPDLCs. Western Blot was performed to evaluate the Wnt/ß-catenin signaling-related protein. Moreover, male Wistar rats model of periodontitis were established to assess the anti-inflammatory and osteoprotective effect of LIRA in vivo. RESULTS: After LIRA treatment, the formation of mineralized nodules was increased, the expression of ALP and Runx2 were upregulated. Moreover, Pg-LPS strongly activated the Wnt/ß-catenin signaling pathway and reduced the osteogenesis of hPDLCs. But these effects were reversed by LIRA. The in vivo results showed that treatment with LIRA resulted in reduced inflammatory cell infiltration in periodontal tissues and decreased concentrations of TNF-α, IL-1ß, and IL-6, and it reduced alveolar bone resorption. CONCLUSIONS: Systemic administration of LIRA solution is a potential treatment for reducing inflammation and bone loss in periodontal disease. This suggests that LIRA can be used as a potential drug for the treatment of periodontitis. CLINICAL SIGNIFICANCE: We showed that systemic administration of LIRA can have a beneficial effect in periodontitis. It can be used as a potential drug for the treatment of periodontitis.