Cargando…

Bone-derived mesenchymal stem cells alleviate compression-induced apoptosis of nucleus pulposus cells by N6 methyladenosine of autophagy

N6 methyladenosine (m(6)A) is one of the most prevalent epitranscriptomic modifications of mRNAs, and plays a critical role in various bioprocesses. Bone-derived mesenchymal stem cells (BMSCs) can attenuate apoptosis of nucleus pulposus cells (NPCs) under compression; however, the underlying mechani...

Descripción completa

Detalles Bibliográficos
Autores principales: Li, Gaocai, Song, Yu, Liao, Zhiwei, Wang, Kun, Luo, Rongjin, Lu, Saideng, Zhao, Kangcheng, Feng, Xiaobo, Liang, Hang, Ma, Liang, Wang, Bingjin, Ke, Wencan, Yin, Huipeng, Zhan, Shengfeng, Li, Shuai, Wu, Xinghuo, Zhang, Yukun, Yang, Cao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7005291/
https://www.ncbi.nlm.nih.gov/pubmed/32029706
http://dx.doi.org/10.1038/s41419-020-2284-8
_version_ 1783494904581718016
author Li, Gaocai
Song, Yu
Liao, Zhiwei
Wang, Kun
Luo, Rongjin
Lu, Saideng
Zhao, Kangcheng
Feng, Xiaobo
Liang, Hang
Ma, Liang
Wang, Bingjin
Ke, Wencan
Yin, Huipeng
Zhan, Shengfeng
Li, Shuai
Wu, Xinghuo
Zhang, Yukun
Yang, Cao
author_facet Li, Gaocai
Song, Yu
Liao, Zhiwei
Wang, Kun
Luo, Rongjin
Lu, Saideng
Zhao, Kangcheng
Feng, Xiaobo
Liang, Hang
Ma, Liang
Wang, Bingjin
Ke, Wencan
Yin, Huipeng
Zhan, Shengfeng
Li, Shuai
Wu, Xinghuo
Zhang, Yukun
Yang, Cao
author_sort Li, Gaocai
collection PubMed
description N6 methyladenosine (m(6)A) is one of the most prevalent epitranscriptomic modifications of mRNAs, and plays a critical role in various bioprocesses. Bone-derived mesenchymal stem cells (BMSCs) can attenuate apoptosis of nucleus pulposus cells (NPCs) under compression; however, the underlying mechanisms are poorly understood. This study showed that the level of m(6)A mRNA modifications was decreased, and the autophagic flux was increased in NPCs under compression when they were cocultured with BMSCs. We report that under coculture conditions, RNA demethylase ALKBH5-mediated FIP200 mRNA demethylation enhanced autophagic flux and attenuated the apoptosis of NPCs under compression. Specific silencing of ALKBH5 results in impaired autophagic flux and a higher proportion of apoptotic NPCs under compression, even when cocultured with BMSCs. Mechanistically, we further identify that the m(6)A “reader” YTHDF2 is likely to be involved in the regulation of autophagy, and lower m(6)A levels in the coding region of FIP200 lead to a reduction in YTHDF2-mediated mRNA degradation of FIP200, a core molecular component of the ULK1 complex that participates in the initiating process of autophagy. Taken together, our study reveals the roles of ALKBH5-mediated FIP200 mRNA demethylation in enhancing autophagy and reducing apoptosis in NPCs when cocultured with BMSCs.
format Online
Article
Text
id pubmed-7005291
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-70052912020-02-10 Bone-derived mesenchymal stem cells alleviate compression-induced apoptosis of nucleus pulposus cells by N6 methyladenosine of autophagy Li, Gaocai Song, Yu Liao, Zhiwei Wang, Kun Luo, Rongjin Lu, Saideng Zhao, Kangcheng Feng, Xiaobo Liang, Hang Ma, Liang Wang, Bingjin Ke, Wencan Yin, Huipeng Zhan, Shengfeng Li, Shuai Wu, Xinghuo Zhang, Yukun Yang, Cao Cell Death Dis Article N6 methyladenosine (m(6)A) is one of the most prevalent epitranscriptomic modifications of mRNAs, and plays a critical role in various bioprocesses. Bone-derived mesenchymal stem cells (BMSCs) can attenuate apoptosis of nucleus pulposus cells (NPCs) under compression; however, the underlying mechanisms are poorly understood. This study showed that the level of m(6)A mRNA modifications was decreased, and the autophagic flux was increased in NPCs under compression when they were cocultured with BMSCs. We report that under coculture conditions, RNA demethylase ALKBH5-mediated FIP200 mRNA demethylation enhanced autophagic flux and attenuated the apoptosis of NPCs under compression. Specific silencing of ALKBH5 results in impaired autophagic flux and a higher proportion of apoptotic NPCs under compression, even when cocultured with BMSCs. Mechanistically, we further identify that the m(6)A “reader” YTHDF2 is likely to be involved in the regulation of autophagy, and lower m(6)A levels in the coding region of FIP200 lead to a reduction in YTHDF2-mediated mRNA degradation of FIP200, a core molecular component of the ULK1 complex that participates in the initiating process of autophagy. Taken together, our study reveals the roles of ALKBH5-mediated FIP200 mRNA demethylation in enhancing autophagy and reducing apoptosis in NPCs when cocultured with BMSCs. Nature Publishing Group UK 2020-02-06 /pmc/articles/PMC7005291/ /pubmed/32029706 http://dx.doi.org/10.1038/s41419-020-2284-8 Text en © The Author(s) 2020 Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Li, Gaocai
Song, Yu
Liao, Zhiwei
Wang, Kun
Luo, Rongjin
Lu, Saideng
Zhao, Kangcheng
Feng, Xiaobo
Liang, Hang
Ma, Liang
Wang, Bingjin
Ke, Wencan
Yin, Huipeng
Zhan, Shengfeng
Li, Shuai
Wu, Xinghuo
Zhang, Yukun
Yang, Cao
Bone-derived mesenchymal stem cells alleviate compression-induced apoptosis of nucleus pulposus cells by N6 methyladenosine of autophagy
title Bone-derived mesenchymal stem cells alleviate compression-induced apoptosis of nucleus pulposus cells by N6 methyladenosine of autophagy
title_full Bone-derived mesenchymal stem cells alleviate compression-induced apoptosis of nucleus pulposus cells by N6 methyladenosine of autophagy
title_fullStr Bone-derived mesenchymal stem cells alleviate compression-induced apoptosis of nucleus pulposus cells by N6 methyladenosine of autophagy
title_full_unstemmed Bone-derived mesenchymal stem cells alleviate compression-induced apoptosis of nucleus pulposus cells by N6 methyladenosine of autophagy
title_short Bone-derived mesenchymal stem cells alleviate compression-induced apoptosis of nucleus pulposus cells by N6 methyladenosine of autophagy
title_sort bone-derived mesenchymal stem cells alleviate compression-induced apoptosis of nucleus pulposus cells by n6 methyladenosine of autophagy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7005291/
https://www.ncbi.nlm.nih.gov/pubmed/32029706
http://dx.doi.org/10.1038/s41419-020-2284-8
work_keys_str_mv AT ligaocai bonederivedmesenchymalstemcellsalleviatecompressioninducedapoptosisofnucleuspulposuscellsbyn6methyladenosineofautophagy
AT songyu bonederivedmesenchymalstemcellsalleviatecompressioninducedapoptosisofnucleuspulposuscellsbyn6methyladenosineofautophagy
AT liaozhiwei bonederivedmesenchymalstemcellsalleviatecompressioninducedapoptosisofnucleuspulposuscellsbyn6methyladenosineofautophagy
AT wangkun bonederivedmesenchymalstemcellsalleviatecompressioninducedapoptosisofnucleuspulposuscellsbyn6methyladenosineofautophagy
AT luorongjin bonederivedmesenchymalstemcellsalleviatecompressioninducedapoptosisofnucleuspulposuscellsbyn6methyladenosineofautophagy
AT lusaideng bonederivedmesenchymalstemcellsalleviatecompressioninducedapoptosisofnucleuspulposuscellsbyn6methyladenosineofautophagy
AT zhaokangcheng bonederivedmesenchymalstemcellsalleviatecompressioninducedapoptosisofnucleuspulposuscellsbyn6methyladenosineofautophagy
AT fengxiaobo bonederivedmesenchymalstemcellsalleviatecompressioninducedapoptosisofnucleuspulposuscellsbyn6methyladenosineofautophagy
AT lianghang bonederivedmesenchymalstemcellsalleviatecompressioninducedapoptosisofnucleuspulposuscellsbyn6methyladenosineofautophagy
AT maliang bonederivedmesenchymalstemcellsalleviatecompressioninducedapoptosisofnucleuspulposuscellsbyn6methyladenosineofautophagy
AT wangbingjin bonederivedmesenchymalstemcellsalleviatecompressioninducedapoptosisofnucleuspulposuscellsbyn6methyladenosineofautophagy
AT kewencan bonederivedmesenchymalstemcellsalleviatecompressioninducedapoptosisofnucleuspulposuscellsbyn6methyladenosineofautophagy
AT yinhuipeng bonederivedmesenchymalstemcellsalleviatecompressioninducedapoptosisofnucleuspulposuscellsbyn6methyladenosineofautophagy
AT zhanshengfeng bonederivedmesenchymalstemcellsalleviatecompressioninducedapoptosisofnucleuspulposuscellsbyn6methyladenosineofautophagy
AT lishuai bonederivedmesenchymalstemcellsalleviatecompressioninducedapoptosisofnucleuspulposuscellsbyn6methyladenosineofautophagy
AT wuxinghuo bonederivedmesenchymalstemcellsalleviatecompressioninducedapoptosisofnucleuspulposuscellsbyn6methyladenosineofautophagy
AT zhangyukun bonederivedmesenchymalstemcellsalleviatecompressioninducedapoptosisofnucleuspulposuscellsbyn6methyladenosineofautophagy
AT yangcao bonederivedmesenchymalstemcellsalleviatecompressioninducedapoptosisofnucleuspulposuscellsbyn6methyladenosineofautophagy