Xianning Zhang , Lulu Liu , Jian Wang , Mingkang Yao , Lei Liu , Haihui Liu , Saisai Ren , Peng Wei , Panpan Cheng , Xiyu Li , Hao Zhang , Mingtai Chen
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Identifying </span>small molecule drugs with role in inhibiting adipogenesis of BM-MSCs may represent a novel direction in AA therapy by improving BM-MSCs mediated marrow microenvironment.</span></p></div><div><h3>Methods</h3><p>For the purpose, we isolated AA BM-MSCs through whole bone marrow cell culture, evaluated a series of small molecule drugs using the in vitro adipogenic differentiation model of BM-MSCs, and finally focused on emodin, a natural anthraquinone derivative. Subsequently, we systematically investigated the molecular mechanism of emodin in attenuating adipogenic process by means of microarray profiling, bioinformatics analysis and lentivirus-mediated functional studies and rescue assay.</p></div><div><h3>Results</h3><p>We found that emodin presented significantly suppressive effect on the in vitro adipogenic differentiation of AA BM-MSCs. Further mechanistic investigation revealed that emodin could increase the expression of Tribbles homolog 3 (TRIB3) which exhibited remarkably decreased expression in AA BM-MSCs compared with the normal counterparts and was subsequently demonstrated as a negative regulator in adipogenesis of AA BM-MSCs. Besides, TRIB3 depletion alleviated the suppressive effect of emodin on the adipogenic differentiation of AA BM-MSCs.</p></div><div><h3>Conclusion</h3><p>Our findings propose that emodin mediated TRIB3 up-regulation alleviates the adipogenic capacity of AA BM-MSCs, and emodin could serve as a potential therapeutic regimen for AA therapy.</p></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"86 ","pages":"Article 102287"},"PeriodicalIF":2.5000,"publicationDate":"2023-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Emodin suppresses adipogenesis of bone marrow derived mesenchymal stem cells from aplastic anemia via increasing TRIB3 expression\",\"authors\":\"Xianning Zhang , Lulu Liu , Jian Wang , Mingkang Yao , Lei Liu , Haihui Liu , Saisai Ren , Peng Wei , Panpan Cheng , Xiyu Li , Hao Zhang , Mingtai Chen\",\"doi\":\"10.1016/j.tice.2023.102287\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p><span>Increasing evidence indicate that enhanced adipogenic differentiation of bone marrow </span>mesenchymal stem cells<span><span> (BM-MSCs) could contribute to the adiposity alteration in marrow microenvironment of aplastic anemia (AA). 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引用次数: 0
摘要
背景越来越多的证据表明，骨髓间充质干细胞（BM-MSCs）的致脂分化增强可能会导致再生障碍性贫血（AA）骨髓微环境的脂肪改变。为此，我们通过全骨髓细胞培养分离了再生障碍性贫血骨髓间充质干细胞，并利用骨髓间充质干细胞体外成脂分化模型评估了一系列小分子药物，最后将研究重点放在了大黄素（一种天然蒽醌衍生物）上。随后，我们通过芯片图谱分析、生物信息学分析、慢病毒介导的功能研究和拯救试验，系统地研究了大黄素抑制成脂过程的分子机制。进一步的机理研究发现，大黄素能增加Tribbles homolog 3（TRIB3）的表达，而TRIB3在AA BM-间充质干细胞中的表达较正常间充质干细胞明显降低，因此被证明是AA BM-间充质干细胞脂肪生成的负调控因子。结论：我们的研究结果表明，大黄素介导的 TRIB3 上调可减轻 AA BM-MSCs 的成脂能力，大黄素可作为治疗 AA 的潜在疗法。
Emodin suppresses adipogenesis of bone marrow derived mesenchymal stem cells from aplastic anemia via increasing TRIB3 expression
Background
Increasing evidence indicate that enhanced adipogenic differentiation of bone marrow mesenchymal stem cells (BM-MSCs) could contribute to the adiposity alteration in marrow microenvironment of aplastic anemia (AA). Identifying small molecule drugs with role in inhibiting adipogenesis of BM-MSCs may represent a novel direction in AA therapy by improving BM-MSCs mediated marrow microenvironment.
Methods
For the purpose, we isolated AA BM-MSCs through whole bone marrow cell culture, evaluated a series of small molecule drugs using the in vitro adipogenic differentiation model of BM-MSCs, and finally focused on emodin, a natural anthraquinone derivative. Subsequently, we systematically investigated the molecular mechanism of emodin in attenuating adipogenic process by means of microarray profiling, bioinformatics analysis and lentivirus-mediated functional studies and rescue assay.
Results
We found that emodin presented significantly suppressive effect on the in vitro adipogenic differentiation of AA BM-MSCs. Further mechanistic investigation revealed that emodin could increase the expression of Tribbles homolog 3 (TRIB3) which exhibited remarkably decreased expression in AA BM-MSCs compared with the normal counterparts and was subsequently demonstrated as a negative regulator in adipogenesis of AA BM-MSCs. Besides, TRIB3 depletion alleviated the suppressive effect of emodin on the adipogenic differentiation of AA BM-MSCs.
Conclusion
Our findings propose that emodin mediated TRIB3 up-regulation alleviates the adipogenic capacity of AA BM-MSCs, and emodin could serve as a potential therapeutic regimen for AA therapy.
期刊介绍：
Tissue and Cell is devoted to original research on the organization of cells, subcellular and extracellular components at all levels, including the grouping and interrelations of cells in tissues and organs. The journal encourages submission of ultrastructural studies that provide novel insights into structure, function and physiology of cells and tissues, in health and disease. Bioengineering and stem cells studies focused on the description of morphological and/or histological data are also welcomed.
Studies investigating the effect of compounds and/or substances on structure of cells and tissues are generally outside the scope of this journal. For consideration, studies should contain a clear rationale on the use of (a) given substance(s), have a compelling morphological and structural focus and present novel incremental findings from previous literature.
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