Phytocannabinoids promote viability and functional adipogenesis of bone marrow-derived mesenchymal stem cells through different molecular targets
Phytocannabinoids promote viability and functional adipogenesis of bone marrow-derived mesenchymal stem cells through different molecular targets
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DOI：
10.1016/j.bcp.2020.113859
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发表时间：
2020-05-01
影响因子：
5.8
通讯作者：
Iannotti, Fabio Arturo
中科院分区：
文献类型：
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作者：
Fellous, Tariq;De Maio, Fabrizia;Iannotti, Fabio Arturo
细胞微环境在骨髓间充质干细胞（BM-MSCs）的维持及其随后的细胞谱系分化中起着关键作用。最近的研究表明，患有脂肪细胞相关代谢紊乱的个体改变了脂肪干细胞亚群（主要是BM-MSC）的功能和成脂潜力，增加了心脏病发作、中风或糖尿病的风险。在这项研究中，我们探讨了一些来自大麻植物的最丰富的非欣快性化合物的潜在治疗作用（或植物大麻素），包括四氢大麻素（THCV）、大麻二酚（CBD）、大麻萜酚（CBG）、大麻二酚酸（CBDA）和大麻萜酚酸（CBGA），通过分析它们对内源性BM-MSC活力的药理学活性以及它们改变BM-MSC增殖和分化成成熟脂肪细胞的能力。我们提供的证据表明，CBD，CBDA，CBGA和THCV（5 μ M）增加了存活的BM-MSC的数量;而只有CBG（5 μ M）和CBD（5 μ M）单独或联合促进BM-MSC成熟为脂肪细胞通过不同的分子机制。这些影响在体外和体内都得到了证实。此外，植物大麻素阻止了由BM-MSC分化的脂肪细胞中棕榈酸酯诱导的胰岛素信号传导障碍。我们的研究强调了植物大麻素作为一种潜在的新型药理学工具，可以在2型糖尿病（T2 DM），衰老和脂肪代谢障碍等代谢紊乱中经常发生的不受调节的能量稳态中重新控制功能性脂肪组织。
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 mu M) increase the number of viable BM-MSCs; whereas only CBG (5 mu M) and CBD (5 mu M) 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.