Anti-Inflammatory and Osteoprotective Effects of Cannabinoid-2 Receptor Agonist HU-308 in a Rat Model of Lipopolysaccharide-Induced Periodontitis

作者：Ossola Cesar A; Surkin Pablo N; Mohn Claudia E; Elverdin Juan C; Fernandez Solari Javier^*

来源：Journal of Periodontology, 2016, 87(6): 725-734.

DOI：10.1902/jop.2016.150612

• Anti-inflammatory agents
• cannabinoid receptor agonists
• lipopolysaccharide
• periodontitis
• saliva

Background: Anti-inflammatory and immunologic properties of cannabinoids have been reported in several tissues. Expression of cannabinoid receptor Type 2 was reported in osteoblasts and osteoclasts, suggesting a key role in bone metabolism. The aim of this study is to assess the effect of treatment with cannabinoid-2 receptor agonist HU-308 in the oral health of rats subjected to lipopolysaccharide (LPS)-induced periodontitis.
Methods: Twenty-four rats were distributed in four groups (six rats per group): 1) control rats; 2) sham rats; 3) rats submitted to experimental periodontitis (LPS); and 4) rats submitted to experimental periodontitis and treated with HU-308 (LPS+HU). In groups LPS and LPS+HU, periodontitis was induced by LPS (1 mg/mL) injected into the gingival tissue (GT) of maxillary and mandibular first molars and into the interdental space between the first and second molars, 3 days per week for 6 weeks. In group LPS+HU, HU-308 (500 ng/mL) was applied topically to the GT daily.
Results: Alveolar bone loss resulting from LPS-induced periodontitis was significantly attenuated with HU-308 treatment (LPS+HU), measured by macroscopic and histologic examination. Treatment also reduced gingival production of inflammatory mediators augmented in LPS-injected rats, such as: 1) inducible nitric oxide (iNOS) activity (LPS: 90.18 +/- 36.51 pmol/minute/mg protein versus LPS+HU: 16.37 +/- 4.73 pmol/minute/mg protein; P < 0.05); 2) tumor necrosis factor alpha (LPS: 185.70 +/- 25.63 pg/mg protein versus LPS+HU: 95.89 +/- 17.47 pg/mg protein; P < 0.05); and 3) prostaglandin E-2 (PGE(2)) (LPS: 159.20 +/- 38.70 pg/mg wet weight versus LPS+HU: 71.25 +/- 17.75 pg/mg wet weight; P < 0.05). Additionally, HU-308 treatment prevented the inhibitory effect of LPS-induced periodontitis on the salivary secretory response to pilocarpine. Moreover, iNOS activity and PGE(2) content, which were increased by LPS-induced periodontitis in the submandibular gland, returned to control values after HU-308 treatment.
Conclusion: This study demonstrates anti-inflammatory, osteoprotective, and prohomeostatic effects of HU-308 in oral tissues of rats with LPS-induced periodontitis.

• 出版日期2016-6