Emodin suppresses adipogenesis of bone marrow derived mesenchymal stem cells from aplastic anemia via increasing TRIB3 expression

  • Tissue Cell. 2023 Dec 10:86:102287. doi: 10.1016/j.tice.2023.102287.
Xianning Zhang  1 ,  Lulu Liu  1 ,  Jian Wang  2 ,  Mingkang Yao  2 ,  Lei Liu  2 ,  Haihui Liu  2 ,  Saisai Ren  2 ,  Peng Wei  3 ,  Panpan Cheng  2 ,  Xiyu Li  4 ,  Hao Zhang  5 ,  Mingtai Chen  6
Affiliations
  • 1. Medical Research Center, Affiliated Hospital of Jining Medical University, Jining 272000, Shandong Province, China.
  • 2. Department of Hematology, Affiliated Hospital of Jining Medical University, Jining 272000, Shandong Province, China.
  • 3. Department of Radiation Oncology, Affiliated Hospital of Jining Medical University, Jining 272000, Shandong Province, China.
  • 4. Department of Graduate School, Jining Medical University, Jining 272000, Shandong Province, China.
  • 5. Department of Hematology, Affiliated Hospital of Jining Medical University, Jining 272000, Shandong Province, China. Electronic address: [email protected].
  • 6. Medical Research Center, Affiliated Hospital of Jining Medical University, Jining 272000, Shandong Province, China. Electronic address: [email protected].
PMID: 38086146 DOI: 10.1016/j.tice.2023.102287
Abstract

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.

Keywords
Adipogenesis; Aplastic anemia; Bone marrow mesenchymal stem cells; Emodin; TRIB3.
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