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多巴胺通过AKT/GSK-3/β-连环蛋白信号通路抑制大鼠骨髓间充质干细胞的成骨分化。

Dopamine Suppresses Osteogenic Differentiation of Rat Bone Marrow-Derived Mesenchymal Stem Cells via AKT/GSK-3/-Catenin Signaling Pathway.

作者信息

Kuang Zhili, Chen Zheng, Tu Shaoqin, Mai Zhihui, Chen Lin, Kang Xiaoning, Chen Xiaochuan, Wei Jiaming, Wang Yuxuan, Peng Yun, Ai Hong

机构信息

Department of Stomatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Department of Stomatology, Huazhong University of Science and Technology Union Shenzhen Hospital (Nanshan Hospital), Shenzhen, China.

出版信息

Stem Cells Int. 2022 Jun 29;2022:4154440. doi: 10.1155/2022/4154440. eCollection 2022.

DOI:10.1155/2022/4154440
PMID:35813889
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9259353/
Abstract

Nervous system is critically involved in bone homeostasis and osteogenesis. Dopamine, a pivotal neurotransmitter, plays a crucial role in sympathetic regulation, hormone secretion, immune activation, and blood pressure regulation. However, the role of dopamine on osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells (rBMSCs) remains poorly understood. In this study, we firstly investigated the effect of dopamine on the apoptosis, proliferation, and osteogenic differentiation of rBMSCs. Dopamine did not, however, interfere with the apoptosis and proliferation of rBMSCs. Interestingly, dopamine suppressed the osteogenic differentiation of rBMSCs, as characterized by reduced ALP staining, ALP activity, mineralized nodule formation, and the mRNA and protein levels of osteogenesis-related genes (, , , , and ). Furthermore, dopamine inactivated AKT/GSK-3/-catenin signaling pathway. Treatment of LiCl (GSK-3 inhibitor) rescued the inhibitory effects of dopamine on osteogenic differentiation of rBMSCs. LY294002 (AKT inhibitor) administration exacerbated the inhibitory effects of dopamine on osteogenic differentiation of rBMSCs. Taken together, these findings indicate that dopamine suppresses osteogenic differentiation of rBMSCs via AKT/GSK-3/-catenin signaling pathway. Our study provides new insights into the role of neurotransmitters in bone homeostasis.

摘要

神经系统在骨稳态和骨生成中起着至关重要的作用。多巴胺作为一种关键的神经递质，在交感神经调节、激素分泌、免疫激活和血压调节中发挥着关键作用。然而，多巴胺对大鼠骨髓间充质干细胞（rBMSCs）成骨分化的作用仍知之甚少。在本研究中，我们首先研究了多巴胺对rBMSCs凋亡、增殖和成骨分化的影响。然而，多巴胺并未干扰rBMSCs的凋亡和增殖。有趣的是，多巴胺抑制了rBMSCs的成骨分化，其特征为碱性磷酸酶（ALP）染色减弱、ALP活性降低、矿化结节形成减少以及成骨相关基因（、、、和）的mRNA和蛋白质水平降低。此外，多巴胺使AKT/GSK-3/β-连环蛋白信号通路失活。用氯化锂（GSK-3抑制剂）处理可挽救多巴胺对rBMSCs成骨分化的抑制作用。给予LY294002（AKT抑制剂）会加剧多巴胺对rBMSCs成骨分化的抑制作用。综上所述，这些发现表明多巴胺通过AKT/GSK-3/β-连环蛋白信号通路抑制rBMSCs的成骨分化。我们的研究为神经递质在骨稳态中的作用提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/623b/9259353/9e00a40297bf/SCI2022-4154440.007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/623b/9259353/9e00a40297bf/SCI2022-4154440.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/623b/9259353/5c96d4676400/SCI2022-4154440.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/623b/9259353/a2aeab461ef5/SCI2022-4154440.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/623b/9259353/855314c1cfa2/SCI2022-4154440.003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/623b/9259353/9e00a40297bf/SCI2022-4154440.007.jpg

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