The Cannabinoid Receptor Type 1 Is Essential for Mesenchymal Stem Cell Survival and Differentiation: Implications for Bone Health

Gowran, Aoife; McKayed, Katey K.; Campbell, Veronica A.

doi:10.1155/2013/796715

Cited by 42 publications

(48 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We have also found that this pro-survival effect of CBD could be mediated by the CB1R. These results are corroborated by other studies which have showing that CB1R activation correlated with reduced apoptosis (Gómez del Pulgar et al, 2000) and increased mesenchymal stem cell survival (Gowran et al, 2013). …”

Section: Discussionsupporting

confidence: 90%

Cannabidiol Modulates the Immunophenotype and Inhibits the Activation of the Inflammasome in Human Gingival Mesenchymal Stem Cells

et al. 2016

View full text Add to dashboard Cite

Human Gingival Mesenchymal Stem Cells (hGMSCs) are multipotential cells that can expand and differentiate in culture under specific and standardized conditions. In the present study, we have investigated whether in vitro pre-treatment of hGMSCs with Cannabidiol (CBD) can influence their expression profile, improving the therapeutic potential of this cell culture. Following CBD treatment (5 μM) for 24 h, gene expression analysis through Next Generation Sequencing (NGS) has revealed several genes differentially expressed between CBD-treated hGMSCs (CBD-hGMSCs) and control cells (CTR-hGMSCs) that were linked to inflammation and apoptosis. In particular, we have demonstrated that CBD treatment in hGMSCs prevented the activation of the NALP3-inflammasome pathway by suppressing the levels of NALP3, CASP1, and IL18, and in parallel, inhibited apoptosis, as demonstrated by the suppression of Bax. CBD treatment was also able to modulate the expression of the well-known mesenchymal stem cell markers (CD13, CD29, CD73, CD44, CD90, and CD166), and other surface antigens. Specifically, CBD led to the downregulation of genes codifying for antigens involved in the activation of the immune system (CD109, CD151, CD40, CD46, CD59, CD68, CD81, CD82, CD99), while it led to the upregulation of those implicated in the inhibition of the immune responses (CD47, CD55, CD276). In conclusion, the present study will provide a new simple and reproducible method for preconditioning hGMSCs with CBD, before transplantation, as an interesting strategy for improving the hGMSCs molecular phenotype, reducing the risk of immune or inflammatory reactions in the host, and in parallel, for increasing their survival and thus, their long-term therapeutic efficacy.

show abstract

Section: Discussionsupporting

confidence: 90%

Cannabidiol Modulates the Immunophenotype and Inhibits the Activation of the Inflammasome in Human Gingival Mesenchymal Stem Cells

et al. 2016

View full text Add to dashboard Cite

show abstract

“…It has previously been reported that CB1 enhances the early osteogenic ability of BMSCs. 22 Meanwhile, the deletion of CB1 causes deossification in mice. 29 Our results are consistent with these findings.…”

Section: Discussionmentioning

confidence: 99%

“…It has been reported that lifetime treatment with the CB1‐specific agonist meth‐AEA (an AEA analogue) significantly attenuates the loss of alveolar bone in a rat periodontitis model . Previous studies have found that CB1 is activated during the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in mice, and CB1 enhances the early osteogenic ability of BMSCs and influences their survival during acute stress . One study has reported that CB1 regulates BMSC migration/homing in mice, and this mediated BMSC function can be enhanced by the CB1‐specific agonists ACEA and weakened by the CB1‐specific antagonist AM281 .…”

Section: Introductionmentioning

confidence: 99%

“…21 Previous studies have found that CB1 is activated during the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in mice, and CB1 enhances the early osteogenic ability of BMSCs and influences their survival during acute stress. 22,23 One study has reported that CB1 regulates BMSC migration/homing in mice, and this mediated BMSC function can be enhanced by the CB1-specific agonists ACEA and weakened by the CB1-specific antagonist AM281. 24 Studies also have reported that CB1 participates in bone regulation and bone metabolism in bone tissue.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

CB1 enhanced the osteo/dentinogenic differentiation ability of periodontal ligament stem cells via p38 MAPK and JNK in an inflammatory environment

et al. 2019

View full text Add to dashboard Cite

Objectives Periodontitis is an inflammatory immune disease that causes periodontal tissue loss. Inflammatory immunity and bone metabolism are closely related to periodontitis. The cannabinoid receptor I (CB1) is an important constituent of the endocannabinoid system and participates in bone metabolism and inflammation tissue healing. It is unclear whether CB1 affects the mesenchymal stem cell (MSC) function involved in periodontal tissue regeneration. In this study, we revealed the role and mechanism of CB1 in the osteo/dentinogenic differentiation of periodontal ligament stem cells (PDLSCs) in an inflammatory environment. Materials and methods Alkaline phosphatase (ALP) activity, Alizarin Red staining, quantitative calcium analysis and osteo/dentinogenic markers were used to assess osteo/dentinogenic differentiation. Real‐time RT‐PCR and Western blotting were employed to detect gene expression. Results CB1 overexpression or CB1 agonist (10 µM R‐1 Meth) promoted the osteo/dentinogenic differentiation of PDLSCs. Deletion of CB1 or the application of CB1 antagonist (10 µM AM251) repressed the osteo/dentinogenic differentiation of PDLSCs. The activation of CB1 enhanced the TNF‐α‐ and INF‐γ‐impaired osteo/dentinogenic differentiation potential in PDLSCs. Moreover, CB1 activated p38 MAPK and JNK signalling and repressed PPAR‐γ and Erk1/2 signalling. Inhibition of JNK signalling could block CB1‐activated JNK and p38 MAPK signalling, while CB1 could activate p38 MAPK and JNK signalling, which was inhibited by TNF‐α and INF‐γ stimulation. Conclusions CB1 was able to enhance the osteo/dentinogenic differentiation ability of PDLSCs via p38 MAPK and JNK signalling in an inflammatory environment, which might be a potential target for periodontitis treatment.

show abstract

“…Indeed, MSCs undergoing osteogenic differentiation have been shown to upregulate CB1 receptors on their surface and activation of CB1 receptors has been reported to positively affect their survival. 43 PEA and DHEA do not mediate their effects via CB1 and CB2. In the central nervous system (CNS), DHEA has been reported to stimulate synaptogenesis and to enhance synaptic connectivity in a CB1-and CB2-independent manner; 44 however, receptors for DHEA still remain to be identified.…”

Section: Discussionmentioning

confidence: 87%

Pharmacological tools to mobilise mesenchymal stromal cells into the blood promote bone formation after surgery

et al. 2020

View full text Add to dashboard Cite

Therapeutic approaches requiring the intravenous injection of autologous or allogeneic mesenchymal stromal cells (MSCs) are currently being evaluated for treatment of a range of diseases, including orthopaedic injuries. An alternative approach would be to mobilise endogenous MSCs into the blood, thereby reducing costs and obviating regulatory and technical hurdles associated with development of cell therapies. However, pharmacological tools for MSC mobilisation are currently lacking. Here we show that β3 adrenergic agonists (β3AR) in combination with a CXCR4 antagonist, AMD3100/Plerixafor, can mobilise MSCs into the blood in mice and rats. Mechanistically we show that reversal of the CXCL12 gradient across the bone marrow endothelium and local generation of endocannabinoids may both play a role in this process. Using a spine fusion model we provide evidence that this pharmacological strategy for MSC mobilisation enhances bone formation.npj Regenerative Medicine (2020) 5:3 ; https://doi.

show abstract

The Cannabinoid Receptor Type 1 Is Essential for Mesenchymal Stem Cell Survival and Differentiation: Implications for Bone Health

Cited by 42 publications

References 37 publications

Cannabidiol Modulates the Immunophenotype and Inhibits the Activation of the Inflammasome in Human Gingival Mesenchymal Stem Cells

Cannabidiol Modulates the Immunophenotype and Inhibits the Activation of the Inflammasome in Human Gingival Mesenchymal Stem Cells

CB1 enhanced the osteo/dentinogenic differentiation ability of periodontal ligament stem cells via p38 MAPK and JNK in an inflammatory environment

Pharmacological tools to mobilise mesenchymal stromal cells into the blood promote bone formation after surgery

Contact Info

Product

Resources

About