title: Anti-Inflammatory and Osteoprotective Effects of Cannabinoid-2 Receptor Agonist HU-308 in a Rat Model of Lipopolysaccharide-Induced Periodontitis.
abstract: 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.
  
  
  
  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.
  
  
  
  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 E2 (PGE2) (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 PGE2 content, which were increased by LPS-induced periodontitis in the submandibular gland, returned to control values after HU-308 treatment.
  
  
  
  This study demonstrates anti-inflammatory, osteoprotective, and prohomeostatic effects of HU-308 in oral tissues of rats with LPS-induced periodontitis.
authors: Department of Physiology, Faculty of Dentistry, University of Buenos Aires, Buenos Aires, Argentina.
authors: Cesar A
authors: CA
authors: Ossola
authors: Department of Physiology, Faculty of Dentistry, University of Buenos Aires, Buenos Aires, Argentina.|National Council of Scientific and Technical Research (CONICET), Buenos Aires, Argentina.
authors: Pablo N
authors: PN
authors: Surkin
authors: Department of Physiology, Faculty of Dentistry, University of Buenos Aires, Buenos Aires, Argentina.|National Council of Scientific and Technical Research (CONICET), Buenos Aires, Argentina.
authors: Claudia E
authors: CE
authors: Mohn
authors: Department of Physiology, Faculty of Dentistry, University of Buenos Aires, Buenos Aires, Argentina.
authors: Juan C
authors: JC
authors: Elverdin
authors: Department of Physiology, Faculty of Dentistry, University of Buenos Aires, Buenos Aires, Argentina.|National Council of Scientific and Technical Research (CONICET), Buenos Aires, Argentina.
authors: Javier
authors: J
authors: Fernández-Solari
mesh_terms: D016301:Alveolar Bone Loss; D000818:Animals; D002186:Cannabinoids / Q000494:pharmacology*; D008070:Lipopolysaccharides; D010518:Periodontitis / Q000178:diet therapy*; D051381:Rats; D043882:Receptors, Cannabinoid
chemical_list: D002186:Cannabinoids; D008070:Lipopolysaccharides; D043882:Receptors, Cannabinoid; C402416:HU 308
keywords: Anti-inflammatory agents; cannabinoid receptor agonists; lipopolysaccharide; periodontitis; saliva