Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 23, Issue 7, Pages -Publisher
MDPI
DOI: 10.3390/ijms23074038
Keywords
metabolic reconfiguration; immunomodulation; periodontal ligament derived stem cells (PDLSCs); mesenchymal stem cells (MSCs); RNA-sequencing (RNA-seq); prostaglandin E2 (PGE2); Indoleamine 2; 3 dioxygenase (IDO)
Funding
- National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services [R00DE025915, R03DE028026, R01DE027901]
- Colgate Palmolive Grant [A-2019-590-OC]
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This study shows that curcumin can enhance the function of periodontal ligament derived stem cells (PDLSC) and increase their immunomodulatory capacity through activation of specific metabolic pathways. It provides a new pharmacological approach to activate endogenous stem cells for immunomodulation and tissue regeneration.
Periodontal ligament derived stem cells (PDLSC) are adult multipotent mesenchymal-like stem cells (MSCs) that can induce a promising immunomodulation to interact with immune cells for disease treatment. Metabolic reconfiguration has been shown to be involved in the immunomodulatory activity of MSCs. However, the underlying mechanisms are largely unknown, and it remains a challenging to establish a therapeutic avenue to enhance immunomodulation of endogenous stem cells for disease management. In the present study, RNA-sequencing (RNA-seq) analysis explores that curcumin significantly promotes PDLSC function through activation of MSC-related markers and metabolic pathways. In vitro stem cell characterization further confirms that self-renewal and multipotent differentiation capabilities are largely elevated in curcumin treated PDLSCs. Mechanistically, RNA-seq reveals that curcumin activates ERK and mTOR cascades through upregulating growth factor pathways for metabolic reconfiguration toward glycolysis. Interestingly, PDLSCs immunomodulation is significantly increased after curcumin treatment through activation of prostaglandin E2-Indoleamine 2,3 dioxygenase (PGE2-IDO) signaling, whereas inhibition of glycolysis activity by 2-deoxyglucose (2-DG) largely blocked immunomodulatory capacity of PDLSCs. Taken together, this study provides a novel pharmacological approach to activate endogenous stem cells through metabolic reprogramming for immunomodulation and tissue regeneration.
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