Association of cannabinoid receptor modulation with normal and abnormal skeletal remodelling: A systematic review and meta-analysis of in vitro, in vivo and human studies

Sophocleous, Antonia; Yiallourides, Michael; Zeng, Fanfei; Pantelas, Pantelis; Stylianou, Eleni; Li, Boya; Carrasco, Giovana; Idris, Aymen I.

doi:10.1016/j.phrs.2021.105928

Cited by 5 publications

(6 citation statements)

References 55 publications

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“…Studies also proposed the reduction of bone resorption during inflammatory disease or even the increase in bone regeneration by stimulating osteoblast formation or by inhibiting osteoclastogenesis through the activation of the receptor system. CB1 and CB2 stimulation and modulation were proposed in the literature to enhance bone formation and increase bone mineral density, however, conflicting data and the need for further studies emerged 38–41 . Data of the present study suggest a different predisposition between recurrent and non‐recurrent patients to respond to the local application of CBs agonists, thus supporting a personalized therapeutic approach to PD.…”

Section: Discussionmentioning

confidence: 62%

Involvement of the endocannabinoid system in current and recurrent periodontitis: A human study

Pellegrini

Carmagnola

Toma

et al. 2023

J of Periodontal Research

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Objective The aim of the present study was to assess if the endocannabinoid system is involved differently in patients with recurrent and non‐recurrent periodontal disease and if in sites that have a predisposition for reactivation, levels of anandamide (AEA) change after periodontal therapy. Background Periodontal disease (PD) may be due to a dysregulation of the endocannabinoid system. Methods Periodontal patients were recruited, treated for PD and monitored. Gingival samples from these patients with recurrent (n = 10) and non‐recurrent (n = 10) periodontal disease were harvested before and after treatment and compared to those of periodontally healthy (n = 10) subjects. Levels of CB1 and CB2, AEA and CBs receptor activation were assessed in healthy and inflamed samples using immunohistochemistry, chromatography and autoradiography. In healed sites, AEA levels were also assessed. Results The number of CBs in inflamed sites of recurrent patients was significantly higher than in those with non‐recurrent disease and also higher than those in healthy subjects. Inflamed sites of recurrent patients had significantly lower CBs receptor activation than those of healthy subjects. Levels of AEA in inflamed sites of non‐recurrent patients were significantly higher than those found both in inflamed recurrent sites and in healthy sites. Otherwise, the amount of AEA in healthy subjects and recurrent inflamed sites was similar. After periodontal therapy, levels of AEA were significantly lower in both periodontal groups. In recurrent sites, they resulted significantly lower than in non‐recurrent and even in healthy subjects. Conclusions The endocannabinoid system seems involved differently in subjects with recurrent and non‐recurrent periodontal disease.

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Section: Discussionmentioning

confidence: 62%

Involvement of the endocannabinoid system in current and recurrent periodontitis: A human study

Pellegrini

Carmagnola

Toma

et al. 2023

J of Periodontal Research

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“…The CB2R activator JWH-133 and antagonist AM630 were employed to determine whether CB2R participates in regulation of the immunophenotype of LPS-treated microglia ( 31 , 32 ). Specifically, the expression patterns of the M1 subtype marker iNOS and M2 subtype marker ARG-1 were determined by IF staining ( Figure 2A ).…”

Section: Resultsmentioning

confidence: 99%

Cannabinoid receptor-2 attenuates neuroinflammation by promoting autophagy-mediated degradation of the NLRP3 inflammasome post spinal cord injury

Jiang

Xia²,

Zhang³

et al. 2022

Front. Immunol.

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BackgroundNeuroinflammation following spinal cord injury (SCI) results in prolonged neurological damage and locomotor dysfunction. Polarization of microglia is vital to regulation of neuroinflammation, although the underlying mechanisms have not yet been elucidated. Endocannabinoid receptor subtype 2 (CB2R) is reported to ameliorate neurodegeneration via immunomodulation activities. However, the underlying machinery in the context of SCI remains unclear.MethodsA lipopolysaccharide-induced microglia inflammation model and a mouse model of SCI were employed to investigate the regulatory role of CB2R in the polarization of microglia in response to excess neuroinflammation. Markers of inflammation and autophagy were measured by Western blot analysis, immunofluorescence, flow cytometry, and enzyme-linked immunosorbent assays. Histological staining with hematoxylin and eosin, Nissl, and Luxol® fast blue was conducted using commercial kits. The locomotor function of the hindlimbs of the experimental mice was evaluated with the Basso Mouse Scale, Louisville Swim Scale, and footprint assay.ResultsThe results showed that CB2R promoted M2 differentiation, increased interleukin (IL)-10 expression, and inhibited M1 differentiation with decreased expression of IL-1β and IL-6. CB2R activation also increased ubiquitination of the NLRP3 inflammasome and interacted with the autophagy-related proteins p62 and microtubule-associated proteins 1B light chain 3. Treatment with the CB2R activator JWH-133 reduced loss of myelin, apoptosis of neurons, and glial scarring, leading to improved functional recovery of the hindlimbs, while the CB2R antagonist AM630 produced opposite results.ConclusionTaken together, these results suggested that CB2R activation attenuated neuroinflammation targeting microglial polarization by promoting NLRP3 clearance, thereby facilitating functional recovery post-SCI.

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“…HU308 as a selective CB2R agonist has been shown to decrease bone loss in an osteoporotic animal model, such as ovariectomized rats and spinal cord injury rats [ 40 ]. In addition, it also exerted a regulatory effect on the osteoblasts and osteoclasts in a CB2R-dependent manner [ 17 , 41 ]. Furthermore, some CB2R agonists from natural products, such as (E)-β-caryophyllene, magnolol, 4-O-methylhonokiol, celastrol, resveratrol, betulinic acid, anthocyanins, and biochanin A have been shown to have potential effects on bone metabolism.…”

Section: Discussionmentioning

confidence: 99%

Identification of Novel Cannabinoid CB2 Receptor Agonists from Botanical Compounds and Preliminary Evaluation of Their Anti-Osteoporotic Effects

Cheng

Zhou

et al. 2022

Molecules

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As cannabinoid CB2 receptors (CB2R) possess various pharmacological effects—including anti-epilepsy, analgesia, anti-inflammation, anti-fibrosis, and regulation of bone metabolism—without the psychoactive side effects induced by cannabinoid CB1R activation, they have become the focus of research and development of new target drugs in recent years. The present study was intended to (1) establish a double luciferase screening system for a CB2R modulator; (2) validate the agonistic activities of the screened compounds on CB2R by determining cAMP accumulation using HEK293 cells that are stably expressing CB2R; (3) predict the binding affinity between ligands and CB2 receptors and characterize the binding modes using molecular docking; (4) analyze the CB2 receptors–ligand complex stability, conformational behavior, and interaction using molecular dynamics; and (5) evaluate the regulatory effects of the screened compounds on bone metabolism in osteoblasts and osteoclasts. The results demonstrated that the screening system had good stability and was able to screen cannabinoid CB2R modulators from botanical compounds. Altogether, nine CB2R agonists were identified by screening from 69 botanical compounds, and these CB2R agonists exhibited remarkable inhibitory effects on cAMP accumulation and good affinity to CB2R, as evidenced by the molecular docking and molecular dynamics. Five of the nine CB2R agonists could stimulate osteoblastic bone formation and inhibit osteoclastic bone resorption. All these findings may provide useful clues for the development of novel anti-osteoporotic drugs and help elucidate the mechanism underlying the biological activities of CB2R agonists identified from the botanical materials.

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Association of cannabinoid receptor modulation with normal and abnormal skeletal remodelling: A systematic review and meta-analysis of in vitro, in vivo and human studies

Cited by 5 publications

References 55 publications

Involvement of the endocannabinoid system in current and recurrent periodontitis: A human study

Involvement of the endocannabinoid system in current and recurrent periodontitis: A human study

Cannabinoid receptor-2 attenuates neuroinflammation by promoting autophagy-mediated degradation of the NLRP3 inflammasome post spinal cord injury

Identification of Novel Cannabinoid CB2 Receptor Agonists from Botanical Compounds and Preliminary Evaluation of Their Anti-Osteoporotic Effects

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