Investigation of in vitro odonto/osteogenic capacity of cannabidiol on human dental pulp cell

Qi, Xia; Liu, Chunyan; Li, Guohua; Luan, Haipei; Li, Shujuan; Yang, Dongru; Zhou, Zheng

doi:10.1016/j.jdent.2021.103673

Cited by 13 publications

(19 citation statements)

References 52 publications

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“…DPSCs also have shown bone regenerative potential. Reports from the literature have shown the anti-inflammatory, antioxidant, antibacterial, and hard/soft tissue regenerative potential of CBD [35][36][37]. However, maintaining the DPSCs' vitality and functions in the inflammatory condition is still a challenge that hinders the application of DPSCs in dentin/pulp and bone regeneration applications.…”

Section: Discussionmentioning

confidence: 99%

“…Since DPSCs are the key cell population in the dental pulp, pulpitis-related inflammation could directly affect the DPSCs survival and functions including odontogenesis, pro-angiogenesis, immunomodulation, etc. [40] Similarly, DPSCs have frequently used seed cells for dentin/pulp revitalization [35,41]. Various drugs and growth factors including BMP2, lithium chloride, etc.…”

Section: Discussionmentioning

confidence: 99%

“…Cannabinoids elicit their activity which acts on two mainly specific G protein-coupled cannabinoid receptors, CB1 and CB2 [32,33]. Recent studies have found that CB1 and CB2 receptors are expressed in dental pulp cells [34,35], and CBD can promote the migration, proliferation, and osteogenic differentiation of mesenchymal stem cells (MSCs). However, whether CBD can promote DPSCs' functions including proliferation, migration, and osteogenic/odontogenic differentiation in pulpitis-related inflammatory milieu has not been investigated yet.…”

Section: Introductionmentioning

confidence: 99%

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Cannabidiol Rescues TNF-α-Inhibited Proliferation, Migration, and Osteogenic/Odontogenic Differentiation of Dental Pulp Stem Cells

Zeng

Zhang

et al. 2023

Biomolecules

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Strategies to promote dental pulp stem cells (DPSCs) functions including proliferation, migration, pro-angiogenic effects, and odontogenic/osteogenic differentiation are in urgent need to restore pulpitis-damaged dentin/pulp regeneration and DPSCs-based bone tissue engineering applications. Cannabidiol (CBD), an active component of Cannabis sativa has shown anti-inflammation, chemotactic, anti-microbial, and tissue regenerative potentials. Based on these facts, this study aimed to analyze the effect of CBD on DPSCs proliferation, migration, and osteogenic/odontogenic differentiation in basal and inflammatory conditions. Highly pure DPSCs with characteristics of mesenchymal stem cells (MSCs) were successfully isolated, as indicated by the results of flowcytometry and multi-lineage (osteogenic, adipogenic, and chondrogenic) differentiation potentials. Among the concentration tested (0.1–12.5 µM), CBD (2.5 μM) showed the highest anabolic effect on the proliferation and osteogenic/odontogenic differentiation of DPSCs. Pro-angiogenic growth factor VEGF mRNA expression was robustly higher in CBD-treated DPSCs. CBD also prompted the migration of DPSCs and CBD receptor CB1 and CB2 expression in DPSCs. TNF-α inhibited the viability, migration, and osteogenic/odontogenic differentiation of DPSCs and CBD reversed these effects. CBD alleviated the TNF-α-upregulated expression of pro-inflammatory cytokines TNF-α, interleukin (IL)-1β, and IL-6 in DPSCs. In conclusion, our results indicate the possible application of CBD on DPSCs-based dentin/pulp and bone regeneration.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Cannabidiol Rescues TNF-α-Inhibited Proliferation, Migration, and Osteogenic/Odontogenic Differentiation of Dental Pulp Stem Cells

Zeng

Zhang

et al. 2023

Biomolecules

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“…Thus, inhibiting inflammation is essential to improve the osteogenic differentiation environment for BMSCs. Recent studies found that CBD, which is already approved by the FDA for refractory epilepsy treatment in children ( 25 ), could promote stem cells odontogenic and osteogenic differentiation ( 26 , 27 ). Additionally, scaffolds combined CBD enhanced mesenchymal stem cell recruitment and regeneration of critical-sized bone defect ( 28 ) in non-inflammatory environment.…”

Section: Discussionmentioning

confidence: 99%

“…Further, p38 MAPK directly regulates downstream osteogenesis-related important target genes, such as Runx2 and osterix ( 37 ). Meanwhile, enhanced ALP activity and osteogenesis-related target genes expression of MSCs were also associated with MAPK activation in non-inflammatory environment ( 26 , 27 ). We found that CBD intervention activated p38 and increased osteogenesis-related mRNA and protein expression levels in inflammatory environment.…”

Section: Discussionmentioning

confidence: 99%

Cannabidiol Promotes Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells in the Inflammatory Microenvironment via the CB2-dependent p38 MAPK Signaling Pathway

Jin

Sun

et al. 2022

Int J Stem Cells

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Background and Objectives: Chronic inflammation of bone tissue often results in bone defects and hazards to tissue repair and regeneration. Cannabidiol (CBD) is a natural cannabinoid with multiple biological activities, including anti-inflammatory and osteogenic potential. This study aimed to investigate the efficacy and mechanisms of CBD in the promotion of bone marrow mesenchymal stem cells (BMSCs) osteogenic differentiation in the inflammatory microenvironment. Methods and Results: BMSCs isolated from C57BL/6 mice, expressed stem cell characteristic surface markers and presented multidirectional differentiation potential. The CCK-8 assay was applied to evaluate the effects of CBD on BMSCs' vitality, and demonstrating the safety of CBD on BMSCs. Then, BMSCs were stimulated with lipopolysaccharide (LPS) to induce inflammatory microenvironment. We found that CBD intervention down-regulated mRNA expression levels of inflammatory cytokines and promoted cells proliferation in LPS-treated BMSCs, also reversed the protein and mRNA levels downregulation of osteogenic markers caused by LPS treatment. Moreover, CBD intervention activated the cannabinoid receptor 2 (CB2) and the p38 mitogen-activated protein kinase (MAPK) signaling pathway. While AM630, a selective CB2 inhibitor, reduced phosphorylated (p)-p38 levels. In addition, AM630 and SB530689, a selective p38 MAPK inhibitor, attenuated the enhancement of osteogenic markers expression levels by CBD in inflammatory microenvironment, respectively. Conclusions: CBD promoted osteogenic differentiation of BMSCs via the CB2/p38 MAPK signaling pathway in the inflammatory microenvironment.

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Cannabidiol-loaded microparticles embedded in a porous hydrogel matrix for biomedical applications

David,

de Souza,

Silva

et al. 2024

J Mater Sci: Mater Med

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In this study, poly (lactic-co-glycolic acid) (PLGA) microparticles loaded with cannabidiol (CBD) were synthesized (PLGA@CBD microparticles) and embedded up to 10 wt% in a chondroitin sulfate/polyvinyl alcohol hydrogel matrix. In vitro chemical, physical, and biological assays were carried out to validate the potential use of the modified hydrogels as biomaterials. The microparticles had spherical morphology and a narrow range of size distribution. CBD encapsulation efficiency was around 52%, loading was approximately 50%. Microparticle addition to the hydrogels caused minor changes in their morphology, FTIR and thermal analyses confirmed these changes. Swelling degree and total porosity were reduced in the presence of microparticles, but similar hydrophilic and degradation in phosphate buffer solution behaviors were observed by all hydrogels. Rupture force and maximum strain at rupture were higher in the modified hydrogels, whereas modulus of elasticity was similar across all materials. Viability of primary human dental pulp cells up to 21 days was generally not influenced by the addition of PLGA@CBD microparticles. The control hydrogel showed no antimicrobial activity against Staphylococcus aureus, whereas hydrogels with 5% and 10% PLGA@CBD microparticles showed inhibition zones. In conclusion, the PLGA@CBD microparticles were fabricated and successfully embedded in a hydrogel matrix. Despite the hydrophobic nature of CBD, the physicochemical and morphological properties were generally similar for the hydrogels with and without the CBD-loaded microparticles. The data reported in this study suggested that this original biomaterial loaded with CBD oil has characteristics that could enable it to be used as a scaffold for tissue/cellular regeneration. Graphical Abstract

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Investigation of in vitro odonto/osteogenic capacity of cannabidiol on human dental pulp cell

Cited by 13 publications

References 52 publications

Cannabidiol Rescues TNF-α-Inhibited Proliferation, Migration, and Osteogenic/Odontogenic Differentiation of Dental Pulp Stem Cells

Cannabidiol Rescues TNF-α-Inhibited Proliferation, Migration, and Osteogenic/Odontogenic Differentiation of Dental Pulp Stem Cells

Cannabidiol Promotes Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells in the Inflammatory Microenvironment via the CB2-dependent p38 MAPK Signaling Pathway

Cannabidiol-loaded microparticles embedded in a porous hydrogel matrix for biomedical applications

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