Transcriptomic analyses of the anti-adipogenic and pro-osteoblastic effects of aspirin in rat bone mesenchymal stem cell

Theoretically, the differentiation of mesenchymal stem cells (MSCs) into either adipocytic or osteoblastic phenotype can be deemed as a seesaw, where induction of one lineage comes at the expense of the other. Previously, researchers, including our team, found that aspirin promoted osteoblast differentiation of bone mesenchymal stem cells (BMSCs) whereas inhibiting adipogenic differentiation. However, the precise mechanisms, that is, which pathways, what biological process or key genes involved during this process, had not been systematically studied. In the present study, we tend to analyze the whole transcriptome of the anti-adipogenic and promote-osteoblastic effects of aspirin in BMSCs. Our results showed that aspirin’s presence restored or further strengthened the expression of an important part of the gene population repressed during adipogenesis or increased during osteogenesis. Besides, classical pathways related to osteogenic differentiation (p53 signaling pathway, focal adhesion, osteoclast differentiation, PI3K-Akt signaling pathway, MAPK signaling pathway, and Wnt signaling pathway) and the fat metabolism were also disturbed during the promote-osteoblastic and anti-adipogenic effects of aspirin. Therefore, our whole-genome transcriptomic results shed new light and open the door to more specific “omics” studies. Our results allow a better understanding of the anti-adipogenic and promote-osteoblastic effects of aspirin and pave the way to aspirin clinical use for the prevention and treatment of diseases like tissue defect and osteoporosis.理论上，间充质干细胞（mesenchymal stem cells, MSCs）向成脂表型或成骨表型的分化可被视为一种跷跷板式的动态平衡，诱导其中一种细胞谱系的分化会以牺牲另一种谱系的分化为代价。此前包括本团队在内的研究人员已发现，阿司匹林可促进骨髓间充质干细胞（bone mesenchymal stem cells, BMSCs）的成骨分化，同时抑制其成脂分化。然而，该过程的精准调控机制——即涉及哪些信号通路、何种生物学过程以及哪些关键基因——尚未得到系统阐释。本研究旨在分析阿司匹林在骨髓间充质干细胞中发挥抗成脂、促成骨作用时的全转录组表达谱。研究结果显示，阿司匹林可恢复或进一步增强成脂过程中被抑制的基因群体，以及成骨过程中表达上调的基因群体中部分关键基因的表达水平。此外，与成骨分化相关的经典信号通路（p53信号通路（p53 signaling pathway）、黏着斑（focal adhesion）、破骨细胞分化（osteoclast differentiation）、PI3K-Akt信号通路（PI3K-Akt signaling pathway）、MAPK信号通路（MAPK signaling pathway）及Wnt信号通路（Wnt signaling pathway））以及脂肪代谢相关通路，在阿司匹林发挥抗成脂与促成骨作用时均发生了显著扰动。因此，本研究的全转录组测序结果为后续更具针对性的“组学”研究提供了全新视角与方向。本研究结果有助于更深入地阐明阿司匹林的抗成脂与促成骨作用机制，为其在组织缺损、骨质疏松等疾病的临床防治中的应用铺平了道路。