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

BACKGROUND: As 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...

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Autores principales: Liu, Xuenan, Lian, Xiaomin, Liu, Xuejiao, Du, Yangge, Zhu, Yuan, Hu, Menglong, Zhang, Ping, Liu, Yunsong, Zhou, Yongsheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261971/
https://www.ncbi.nlm.nih.gov/pubmed/34233738
http://dx.doi.org/10.1186/s13287-021-02425-3
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author Liu, Xuenan
Lian, Xiaomin
Liu, Xuejiao
Du, Yangge
Zhu, Yuan
Hu, Menglong
Zhang, Ping
Liu, Yunsong
Zhou, Yongsheng
author_facet Liu, Xuenan
Lian, Xiaomin
Liu, Xuejiao
Du, Yangge
Zhu, Yuan
Hu, Menglong
Zhang, Ping
Liu, Yunsong
Zhou, Yongsheng
author_sort Liu, Xuenan
collection PubMed
description BACKGROUND: As 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. METHODS: Lost-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. RESULTS: Our 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. CONCLUSIONS: Collectively, 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-021-02425-3.
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spelling pubmed-82619712021-07-07 Aldo-keto reductase family 1 member C1 regulates the osteogenic differentiation of human ASCs by targeting the progesterone receptor Liu, Xuenan Lian, Xiaomin Liu, Xuejiao Du, Yangge Zhu, Yuan Hu, Menglong Zhang, Ping Liu, Yunsong Zhou, Yongsheng Stem Cell Res Ther Research BACKGROUND: As 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. METHODS: Lost-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. RESULTS: Our 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. CONCLUSIONS: Collectively, 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-021-02425-3. BioMed Central 2021-07-07 /pmc/articles/PMC8261971/ /pubmed/34233738 http://dx.doi.org/10.1186/s13287-021-02425-3 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Liu, Xuenan
Lian, Xiaomin
Liu, Xuejiao
Du, Yangge
Zhu, Yuan
Hu, Menglong
Zhang, Ping
Liu, Yunsong
Zhou, Yongsheng
Aldo-keto reductase family 1 member C1 regulates the osteogenic differentiation of human ASCs by targeting the progesterone receptor
title Aldo-keto reductase family 1 member C1 regulates the osteogenic differentiation of human ASCs by targeting the progesterone receptor
title_full Aldo-keto reductase family 1 member C1 regulates the osteogenic differentiation of human ASCs by targeting the progesterone receptor
title_fullStr Aldo-keto reductase family 1 member C1 regulates the osteogenic differentiation of human ASCs by targeting the progesterone receptor
title_full_unstemmed Aldo-keto reductase family 1 member C1 regulates the osteogenic differentiation of human ASCs by targeting the progesterone receptor
title_short Aldo-keto reductase family 1 member C1 regulates the osteogenic differentiation of human ASCs by targeting the progesterone receptor
title_sort aldo-keto reductase family 1 member c1 regulates the osteogenic differentiation of human ascs by targeting the progesterone receptor
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261971/
https://www.ncbi.nlm.nih.gov/pubmed/34233738
http://dx.doi.org/10.1186/s13287-021-02425-3
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