Signs of alveolar bone damage in early stages of periodontitis and its prevention by stimulation of cannabinoid receptor 2. Model in rats

Abstract

The aims of the present study were, first, to identify signs of alveolar bone damage in early stages of experimental periodontitis (EP) and, second, to assess its possible prevention by treatment with cannabinoid receptor 2 agonist HU 308. Experimental periodontitis was induced by injections of lipopolysaccharide (LPS) (1mg/ml) in gums surrounding maxillary and mandibular first molar, 3 days per week, and untreated controls were kept for comparison. Then, a 3-week study was conducted including eighteen new rats (six rats per group): 1) controls; 2) experimental periodontitis rats; and 3) experimental periodontitis rats treated daily with HU 308 (500 ng/ml). After euthanasia, alveolar bone loss was assessed by morphometric and histomorphometric techniques, and the content of prostaglandin E2 (PGE2) in gingival tissue was evaluated by radioimmunoassay. The first signs of alveolar bone loss were apparent at 3 weeks of experimental periodontitis (ρ<0.05) in the mandibular first molar, but there was no detectable change at 1 week, leading us to establish 3 weeks as an early stage of experimental periodontitis. Rats subjected to 3-week experimental periodontitis showed less interradicular bone volume, less whole bone perimeter and fewer bone formation areas, and higher periodontal space height, bone resorption areas, number of osteoclasts and gingival content of prostaglandin E2 than controls, while HU 308 prevented, at least partially, the deleterious effects (ρ<0.001). We can conclude that a 3-week term of lipopolysaccharide-induced periodontitis in rats provides a valid model of the early stage of the disease, as emerging damage is observed in bone tissue. Furthermore, harmful effects at 3 weeks could be prevented by local stimulation of cannabinoid receptor 2, before greater damage is produced.

A critical review of cannabis in medicine and dentistry: A look back and the path forward

“…Moreover, other related findings showed that HU‐308 has prohomeostasis effects by inducing anti‐inflammatory and osteoprotective properties in oral tissues of rats with LPS‐induced PD (Ossola et al, 2016 ). These studies, along with others (Ossola et al, 2020 ; Zhang et al, 2020 ), highlight the important role of the ECS in oral and systemic health. Moreover, the cytokine and chemokine inhibition profiles of HU‐308 (agonist) and SMM‐189 (inverse agonist) were investigated in activated hPDLFs, and study results showed that CB2R ligands are viable candidates for the development of a new therapeutic intervention for PD (Figure 2 ) (Abidi et al, 2020 ).…”

Cannabinoids in Periodontology: Where Are We Now?

“…These findings indicate the potential role of CB1 in mesenchymal stem cells and periodontal regeneration, making it a promising target for bone regeneration [105]. In contrast, CB2 activation has been reported to reduce alveolar bone loss in rats with periodontal disease [106]. Additionally, THC in periodontal fibroblasts promotes adhesion and migration, primarily through CB2 activation [88].…”

Endocannabinoid system and periodontitis: mechanisms and therapeutic implications

“…The presence of both AEA and 2-AG, as other endocannabinoids, with their distinct affinities and receptor interactions, enables the ECS to finely tune cellular responses to maintain homeostasis and adapt to external challenges 13 . The use of phytocannabinoids or synthetic cannabinoids is also a therapeutic possibility in PD treatment under investigation 24,27,30,32,33,37,[40][41][42][43] . Pre-clinical studies have demonstrated that systemic or local application of different cannabinoids (Table 1) might mimic endocannabinoids action and interact with both CB1 and CB2 in periodontitis models in vitro and in vivo 24,33 .…”