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Article

Modulation of Endocannabinoid Tone in Osteoblastic Differentiation of MC3T3-E1 Cells and in Mouse Bone Tissue over Time

1
Endocannabinoid Research Group, Institute of Biomolecular Chemistry (ICB), National Research Council of Italy, 80078 Pozzuoli, Italy
2
Institute of Genetics and Biophysics Adriano Buzzati-Traverso, National Research Council of Italy, 80131 Naples, Italy
*
Author to whom correspondence should be addressed.
Academic Editor: Annalisa Santucci
Cells 2021, 10(5), 1199; https://doi.org/10.3390/cells10051199
Received: 19 March 2021 / Revised: 6 May 2021 / Accepted: 10 May 2021 / Published: 14 May 2021
Bone is a highly complex and metabolically active tissue undergoing a continuous remodeling process, which endures throughout life. A complex cell-signaling system that plays role in regulating different physiological processes, including bone remodeling, is the endocannabinoid system (ECS). Bone mass expresses CB1 and CB2 cannabinoid receptors and enzymatic machinery responsible for the metabolism of their endogenous ligands, endocannabinoids (AEA and 2-AG). Exogenous AEA is reported to increase the early phase of human osteoblast differentiation in vitro. However, regarding this cell context little is known about how endocannabinoids and endocannabinoid-related N-acylethanolamines like PEA and OEA are modulated, in vitro, during cell differentiation and, in vivo, over time up to adulthood. Here we characterized the endocannabinoid tone during the different phases of the osteoblast differentiation process in MC3T3-E1 cells, and we measured endocannabinoid levels in mouse femurs at life cycle stages characterized by highly active bone growth (i.e., of juvenile, young adult, and mature adult bone). Endocannabinoid tone was significantly altered during osteoblast differentiation, with substantial OEA increment, decline in 2-AG and AEA, and consistent modulation of their metabolic enzymes in maturing and mineralized MC3T3-E1 cells. Similarly, in femurs, we found substantial, age-related, decline in 2-AG, OEA, and PEA. These findings can expand existing knowledge underlying physiological bone cell function and contribute to therapeutic strategies for preventing bone-related metabolic changes accruing through lifespan. View Full-Text
Keywords: bone; osteoblasts; endocannabinoids; N-acylethanolamines; MC3T3-E1 bone; osteoblasts; endocannabinoids; N-acylethanolamines; MC3T3-E1
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MDPI and ACS Style

Kostrzewa, M.; Mahmoud, A.M.; Verde, R.; Scotto di Carlo, F.; Gianfrancesco, F.; Piscitelli, F.; Ligresti, A. Modulation of Endocannabinoid Tone in Osteoblastic Differentiation of MC3T3-E1 Cells and in Mouse Bone Tissue over Time. Cells 2021, 10, 1199. https://doi.org/10.3390/cells10051199

AMA Style

Kostrzewa M, Mahmoud AM, Verde R, Scotto di Carlo F, Gianfrancesco F, Piscitelli F, Ligresti A. Modulation of Endocannabinoid Tone in Osteoblastic Differentiation of MC3T3-E1 Cells and in Mouse Bone Tissue over Time. Cells. 2021; 10(5):1199. https://doi.org/10.3390/cells10051199

Chicago/Turabian Style

Kostrzewa, Magdalena, Ali M. Mahmoud, Roberta Verde, Federica Scotto di Carlo, Fernando Gianfrancesco, Fabiana Piscitelli, and Alessia Ligresti. 2021. "Modulation of Endocannabinoid Tone in Osteoblastic Differentiation of MC3T3-E1 Cells and in Mouse Bone Tissue over Time" Cells 10, no. 5: 1199. https://doi.org/10.3390/cells10051199

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