Chidamide suppresses adipogenic differentiation of bone marrow derived mesenchymal stem cells via increasing REEP2 expression

Xianning Zhang; Lulu Liu; Xin Liu; Qian Huang; Lei Liu; Haihui Liu; Saisai Ren; Peng Wei; Panpan Cheng; Mingkang Yao; Wenjun Song; Hao Zhang; Mingtai Chen

doi:10.1016/j.isci.2023.106221

Chidamide suppresses adipogenic differentiation of bone marrow derived mesenchymal stem cells via increasing REEP2 expression

iScience. 2023 Feb 16;26(3):106221. doi: 10.1016/j.isci.2023.106221. eCollection 2023 Mar 17.

Authors

Xianning Zhang¹, Lulu Liu¹, Xin Liu², Qian Huang³, Lei Liu³, Haihui Liu³, Saisai Ren³, Peng Wei⁴, Panpan Cheng³, Mingkang Yao², Wenjun Song², Hao Zhang³, Mingtai Chen¹

Affiliations

¹ Medical Research Center, Affiliated Hospital of Jining Medical University, Jining 272000, Shandong Province, China.
² Department of Graduate School, Jining Medical University, Jining 272000, Shandong Province, China.
³ Department of Hematology, Affiliated Hospital of Jining Medical University, Jining 272000, Shandong Province, China.
⁴ Department of Radiation Oncology, Affiliated Hospital of Jining Medical University, Jining 272000, Shandong Province, China.

Abstract

Increased propensity of bone marrow-derived mesenchymal stem cells (BM-MSCs) toward adipogenic differentiation at the expense of osteogenesis has been implicated in obesity, diabetes, and age-related osteoporosis as well as various hematopoietic disorders. Defining small molecules with role in rectifying the adipo-osteogenic differentiation imbalance is of great significance. Here, we unexpectedly found that Chidamide, a selective histone deacetylases inhibitor, exhibited remarkably suppressive effect on the in vitro induced adipogenic differentiation of BM-MSCs. Multifaceted alterations in the spectrum of gene expression were observed in Chidamide-managed BM-MSCs during adipogenic induction. Finally, we focused on REEP2, which presented decreased expression in BM-MSCs-mediated adipogenesis and was restored by Chidamide treatment. REEP2 was subsequently demonstrated as a negative regulator of adipogenic differentiation of BM-MSCs and mediated the suppressive effect of Chidamide on adipocyte development. Our findings provide the theoretical and experimental foundation for the clinical application of Chidamide for disorders associated with excessive marrow adipocytes.

Keywords: Biological sciences; Molecular biology; Molecular mechanism of gene regulation; Stem cells research.