Phytocannabinoids promote viability and functional adipogenesis of bone marrow-derived mesenchymal stem cells through different molecular targets
| Autor: | Fabio Arturo Iannotti, Tariq Fellous, Fabrizia De Maio, Biagio Carannante, Hilal Kalkan, Stefania Petrosino, Sabatino Maione, Vincenzo Di Marzo, Serena Boccella |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cell Survival Cannabigerol Adipose tissue Bone Marrow Cells Biology Tetrahydrocannabivarin Biochemistry Energy homeostasis Colony-Forming Units Assay Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Adipocytes medicine Animals Insulin Cells Cultured Triglycerides Cannabis Pharmacology Adipogenesis Cannabinoids Mesenchymal stem cell Cell Differentiation Mesenchymal Stem Cells Fibroblasts Cell biology Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure chemistry 030220 oncology & carcinogenesis Female Bone marrow Stem cell Energy Metabolism Endocannabinoids medicine.drug |
| Zdroj: | Biochemical Pharmacology. 175:113859 |
| ISSN: | 0006-2952 |
| DOI: | 10.1016/j.bcp.2020.113859 |
| Popis: | The cellular microenvironment plays a critical role in the maintenance of bone marrow-derived mesenchymal stem cells (BM-MSCs) and their subsequent cell lineage differentiation. Recent studies suggested that individuals with adipocyte-related metabolic disorders have altered function and adipogenic potential of adipose stem cell subpopulations, primarily BM-MSCs, increasing the risk of heart attack, stroke or diabetes. In this study, we explored the potential therapeutic effect of some of the most abundant non-euphoric compounds derived from the Cannabis sativa plant (or phytocannabinoids) including tetrahydrocannabivarin (THCV), cannabidiol (CBD), cannabigerol (CBG), cannabidiolic acid (CBDA) and cannabigerolic acid (CBGA), by analysing their pharmacological activity on viability of endogenous BM-MSCs as well as their ability to alter BM-MSC proliferation and differentiation into mature adipocytes. We provide evidence that CBD, CBDA, CBGA and THCV (5 µM) increase the number of viable BM-MSCs; whereas only CBG (5 µM) and CBD (5 µM) alone or in combination promote BM-MSCs maturation into adipocytes via distinct molecular mechanisms. These effects were revealed both in vitro and in vivo. In addition, phytocannabinoids prevented the insulin signalling impairment induced by palmitate in adipocytes differentiated from BM-MSCs. Our study highlights phytocannabinoids as a potential novel pharmacological tool to regain control of functional adipose tissue in unregulated energy homeostasis often occurring in metabolic disorders including type 2 diabetes mellitus (T2DM), aging and lipodystrophy. |
| Databáze: | OpenAIRE |
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