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Ferulic acid improves self‐renewal and differentiation of human tendon‐derived stem cells by upregulating early growth response 1 through hypoxia
Author(s) -
Qiu Shuo,
Sun Yunchu,
Xu Jia,
Wen Gen,
Yu Yaling,
Wu Tianyi,
Chai Yimin
Publication year - 2019
Publication title -
genesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.093
H-Index - 110
eISSN - 1526-968X
pISSN - 1526-954X
DOI - 10.1002/dvg.23291
Subject(s) - runx2 , adipogenesis , stem cell , hypoxia (environmental) , microbiology and biotechnology , luciferase , western blot , transactivation , biology , egr1 , downregulation and upregulation , transcription factor , chemistry , transfection , andrology , cell culture , mesenchymal stem cell , biochemistry , medicine , genetics , gene , organic chemistry , oxygen
Summary We aimed to investigate the potential beneficial effect of ferulic acid (FA) on stemness of human tendon‐derived stem cells (hTSCs) in vitro and to elucidate the underlying molecular mechanism. The self‐renewal ability of hTSCs was evaluated by colony formation and cell proliferation was determined by CCK‐8 kit. Adipogenesis, osteogenesis, and chondrogenesis were determined by Oil Red O, Alizarin Red, and Alcian Blue stainings, respectively. Relative mRNA levels of PPARγ, Col2A1, Acan, Runx2, HIF1α, and EGR1 were measured with real‐time PCR. Protein levels of HIF1α and EGR1 were detected by western blot. Direct binding of HIF1α with EGR1 promoter was analyzed by ChIP assay. Hypoxia‐induced expression of EGR1 was interrogated by luciferase reporter assay. We demonstrated that FA treatment improved both self‐renewal ability and multi‐differentiation potential of hTSCs. FA induced hypoxia which in turn upregulated EGR1 expression via direct association with its hypoxia response element consensus sequence. Furthermore, we showed that both HIF1α and EGR1 were required for the enhancing effects of FA on hTSC self‐renewal and differentiation. We hereby characterize the beneficial effect of FA on the stemness of hTSCs and highlight the critical role of HIF1α‐EGR1 axis in this process.