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

Ossola, Cesar Angel; Surkin, Pablo N.; Mohn, Claudia; Elverdín, Juan C.; Fernández‐Solari, Javier

doi:10.1902/jop.2016.150612

Cited by 55 publications

(81 citation statements)

References 50 publications

(109 reference statements)

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“…Additionally, cannabidiol has been involved in the promotion of mesenchymal cells migration and osteoblastic differentiation through the activation of CB2r and the inhibition of GPR55, while AM630 abolished the effects of cannabidiol . Overall, these results are consistent with our previous studies, where stimulation of CB1r and CB2r with meth‐AEA and HU308, respectively, produced a marked reduction in the inflammatory mediators in gingival tissue and ABL . According to the current study, the blockage of specific cannabinoid receptors avoids the binding of endogenous ligands which are increased under inflammatory conditions, and the activation of subsequent intracellular pathways.…”

Section: Discussionsupporting

confidence: 92%

“…Although the effects of the activation of the ECS are complex and remain subjected to continuous research, many in vivo and in vitro studies have demonstrated that the stimulation of CB1r as well as CB2r reduces the level of inflammatory mediators and bone resorption in animal tissues . ‒ In previous studies of our group, inflammation in gums and ABL have been prevented by the CB1r and CB2r separate activation, but there is no record of the complete blockage of specific cannabinoid receptors.…”

Section: Introductionmentioning

confidence: 77%

“…‒ Most of these studies have approached this issue through cells cultures such as human gingival fibroblasts and ligament periodontal cells . However, our research group reported anti‐inflammatory effects on gingival tissue and osteoprotective effects on alveolar bone induced by both a CB2r and a CB1r agonist (HU308 and meth‐AEA, respectively), in a model of LPS‐induced periodontal disease in vivo …”

Section: Discussionmentioning

confidence: 97%

“…Regarding PGE 2 and TNF‐α, it has been demonstrated that they are two of the main inflammatory mediators involved in bone resorption activity, mainly through modulation of RANK, RANKL, and osteoclasts function . Moreover, the reduction of their levels in periodontal tissues by using anti‐inflammatory agents was reported to attenuate ABL …”

Section: Discussionmentioning

confidence: 99%

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A new target to ameliorate the damage of periodontal disease: The role of transient receptor potential vanilloid type‐1 in contrast to that of specific cannabinoid receptors in rats

Ossola

Balcarcel

Astrauskas

et al. 2019

Journal of Periodontology

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Background Transient receptor potential vanilloid type‐1 (TRPV1) is expressed in oral tissues cells and its activity can be regulated by inflammation products and anandamide. The aim of the present study was to evaluate the effects of blocking TRPV1 or specific cannabinoid receptors 1 (CB1r) and 2 (CB2r) on periodontal status of rats subjected to experimental periodontitis (EP). Methods Male rats were distributed in groups 1) control, 2) lipopolysaccharide‐induced EP (LPS), and 3) LPS plus capsazepine (Capz, TRPV1 antagonist) application (LPS+Capz). EP was induced by injections of LPS (1 mg/mL) around first molars and treatment was performed with Capz (2 µg/mL) applied locally during 6 weeks. Additional experiment was performed by applying CB1r and CB2r antagonists (AM251 and AM630) to rats with EP. Results Capz prevented alveolar bone loss (ABL) on the external crests and in the interradicular bone of the first molars (periodontal space height: LPS, 270.7 ± 33.5µm versus LPS+Capz, 216.4 ± 19.9 µm; P <0.01). Inflammatory mediators, like tumor necrosis factor‐alpha and prostaglandin E2, increased by LPS‐induced EP, were diminished in gingival tissue of rats treated with Capz. In contrast, application of AM251 and AM630 exacerbated ABL and gingival inflammatory mediators, increased by LPS, altering also biomechanical properties. Conclusions TRPV1 blockade attenuates periodontal impairment in EP rats, since it reduces local inflammation, unlike CB1r and CB2r blockade. This work lays the foundation for developing therapeutics in humans based on the pharmacological manipulation of these receptors to treat periodontal disease.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

A new target to ameliorate the damage of periodontal disease: The role of transient receptor potential vanilloid type‐1 in contrast to that of specific cannabinoid receptors in rats

Ossola

Balcarcel

Astrauskas

et al. 2019

Journal of Periodontology

Self Cite

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“…iNOS‐derived NO can lead to the destruction of collagen fibers via up‐regulated matrix metalloproteinases and apical migration of the junctional epithelium . It has been reported that the level of iNOS is higher in gingiva with periodontitis is higher than in healthy gingiva . Also, iNOS levels increase with severe inflammation in periodontal tissues .…”

Section: Discussionmentioning

confidence: 99%

Effects of rosuvastatin on inducible nitric oxide synthase in rats with hyperlipidaemia and periodontitis

Kırzıoğlu

Özmen

Doğan

et al. 2017

J of Periodontal Research

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Administration of rosuvastatin reduced gingival iNOS expression in ligature-induced periodontitis with/without hyperlipidaemia. It also led to significant differences in ABL in rats with periodontitis, except when periodontitis was associated with hyperlipidaemia. These findings could provide an important contribution in further studies to evaluate the role of rosuvastatin as a host modulatory agent in the pathogenesis of periodontal diseases.

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Effects of O‐methylated (−)‐epigallocatechin gallate (EGCG) on LPS‐induced osteoclastogenesis, bone resorption, and alveolar bone loss in mice

et al. 2017

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(−)‐Epigallocatechin‐3‐ O ‐gallate ( EGCG ), present in green tea, exhibits antioxidant and antiallergy effects. EGCG 3″Me, a 3‐ O ‐methylated derivative of EGCG , has been reported to show similar biological functions; the inhibitory activity of EGCG 3″Me in a mouse allergy model was more potent than that of EGCG , probably due to the efficiency of absorption from the intestine. However, the functional potency of these EGCG s is controversial in each disease model. We previously observed that EGCG suppressed inflammatory bone resorption and prevented alveolar bone loss in a mouse model of periodontosis. In this study, we examined the role of EGCG 3″Me in bone resorption using a mouse model of periodontitis. Lipopolysaccharide ( LPS )‐induced osteoclast formation was suppressed by adding EGCG 3″Me to cocultures of osteoblasts and bone marrow cells, and LPS ‐induced bone resorption was also inhibited by EGCG 3″Me in calvarial organ cultures. EGCG 3″Me acted on osteoblasts and suppressed prostaglandin E ( PGE ) production, which is critical for inflammatory bone resorption, by inhibiting the expression of COX ‐2 and mPGES ‐1, key enzymes for PGE synthesis. In osteoclast precursor macrophages, EGCG 3″Me suppressed RANKL ‐dependent differentiation into mature osteoclasts. In a mouse model of periodontitis, LPS ‐induced bone resorption was suppressed by EGCG 3″Me in organ culture of mouse alveolar bone, and the alveolar bone loss was further attenuated by the treatment of EGCG 3″Me in the lower gingiva in vivo . EGCG 3″Me may be a potential natural compound for the protection of inflammatory bone loss in periodontitis.

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

Abstract: This study demonstrates anti-inflammatory, osteoprotective, and prohomeostatic effects of HU-308 in oral tissues of rats with LPS-induced periodontitis.

Cited by 55 publications

References 50 publications

A new target to ameliorate the damage of periodontal disease: The role of transient receptor potential vanilloid type‐1 in contrast to that of specific cannabinoid receptors in rats

A new target to ameliorate the damage of periodontal disease: The role of transient receptor potential vanilloid type‐1 in contrast to that of specific cannabinoid receptors in rats

Effects of rosuvastatin on inducible nitric oxide synthase in rats with hyperlipidaemia and periodontitis

Effects of O‐methylated (−)‐epigallocatechin gallate (EGCG) on LPS‐induced osteoclastogenesis, bone resorption, and alveolar bone loss in mice

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