Aldo-keto reductase family 1 member C1 regulates the osteogenic differentiation of human ASCs by targeting the progesterone receptor

Stem Cell Research & Therapy

Xuejiao Liu¹  Yangge Du¹  Yunsong Liu¹  Xuenan Liu¹  Ping Zhang¹  Yuan Zhu¹  Menglong Hu¹  Xiaomin Lian¹  Yongsheng Zhou¹ 

[1] Department of Prosthodontics, Peking University School and Hospital of Stomatology, National Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, National Clinical Research Center for Oral Diseases, 22 Zhongguancun South Avenue, 100081, Beijing, People’s Republic of China;

关键词: AKR1C1;    Osteogenesis;    Adipose-derived mesenchymal stromal/stem cells;    Progesterone receptor;   

DOI  :  10.1186/s13287-021-02425-3

来源: Springer

【 摘 要 】

BackgroundAs a promising way to repair bone defect, bone tissue engineering has attracted a lot of attentions from researchers in recent years. Searching for new molecular target to modify the seed cells and enhance their osteogenesis capacity is one of the hot topics in this field. As a member of aldo-keto reductase family, aldo-keto reductase family 1 member C1 (AKR1C1) is reported to associate with various tumors. However, whether AKR1C1 takes part in regulating differentiation of adipose-derived mesenchymal stromal/stem cells (ASCs) and its relationship with progesterone receptor (PGR) remain unclear.MethodsLost-and-gain-of-function experiments were performed using knockdown and overexpression of AKR1C1 to identify its role in regulating osteogenic and adipogenic differentiation of hASCs in vitro. Heterotypic bone and adipose tissue formation assay in nude mice were used to conduct the in vivo experiment. Plasmid and siRNA of PGR, as well as western blot, were used to clarify the mechanism AKR1C1 regulating osteogenesis.ResultsOur results demonstrated that AKR1C1 acted as a negative regulator of osteogenesis and a positive regulator of adipogenesis of hASCs via its enzyme activity both in vitro and in vivo. Mechanistically, PGR mediated the regulation of AKR1C1 on osteogenesis.ConclusionsCollectively, our study suggested that AKR1C1 could serve as a regulator of osteogenic differentiation via targeting PGR and be used as a new molecular target for ASCs modification in bone tissue engineering.

【 授权许可】

CC BY