Cargando…

Polycystin-2 mediates mechanical tension-induced osteogenic differentiation of human adipose-derived stem cells by activating transcriptional co-activator with PDZ-binding motif

Human adipose-derived stem cells (hASCs) have multi-directional differentiation potential including osteogenic differentiation. Mechanical stimulation is thought to be a key regulator of bone remodeling and has been proved to promote osteogenic differentiation of mesenchymal stem cells. However, the...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Liang, Lu, Yahui, Cai, Guanhui, Chen, Hongyu, Li, Gen, Liu, Luwei, Sun, Lian, Guan, Zhaolan, Sun, Wen, Zhao, Chunyang, Wang, Hua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9450996/
https://www.ncbi.nlm.nih.gov/pubmed/36091380
http://dx.doi.org/10.3389/fphys.2022.917510
_version_ 1784784644686741504
author Wang, Liang
Lu, Yahui
Cai, Guanhui
Chen, Hongyu
Li, Gen
Liu, Luwei
Sun, Lian
Guan, Zhaolan
Sun, Wen
Zhao, Chunyang
Wang, Hua
author_facet Wang, Liang
Lu, Yahui
Cai, Guanhui
Chen, Hongyu
Li, Gen
Liu, Luwei
Sun, Lian
Guan, Zhaolan
Sun, Wen
Zhao, Chunyang
Wang, Hua
author_sort Wang, Liang
collection PubMed
description Human adipose-derived stem cells (hASCs) have multi-directional differentiation potential including osteogenic differentiation. Mechanical stimulation is thought to be a key regulator of bone remodeling and has been proved to promote osteogenic differentiation of mesenchymal stem cells. However, the mechanism how mechanical tension-induced osteogenesis of hASCs still remains poor understood. Polycystin-2 (PC2), a member of the transient receptor potential polycystic (TRPP) family, is involved in cilia-mediated mechanical transduction. To understand the role of PC2 in osteogenic differentiation under mechanical stimuli in hASCs, PKD2 gene was stably silenced by using lentivirus-mediated shRNA technology. The results showed that mechanical tension sufficiently enhanced osteogenic differentiation but hardly affected proliferation of hASCs. Silencing PKD2 gene caused hASCs to lose the ability of sensing mechanical stimuli and subsequently promoting osteogenesis. PC2 knock-out also reduced the cilia population frequency and cilia length in hASCs. TAZ (transcriptional coactivator with PDZ-binding motif, also known as Wwtr1) could mediate the genes regulation and biological functions of mechanotransduction signal pathway. Here, mechanical tension also enhanced TAZ nuclear translocation of hASCs. PC2 knock-out blocked tension-induced upregulation of nuclear TAZ and suppress tension-induced osteogenesis. TAZ could directly interact with Runx2, and inhibiting TAZ could suppress tension-induced upregulation of Runx2 expression. In summary, our findings demonstrated that PC2 mediate mechanical tension-induced osteogenic differentiation of hASCs by activating TAZ.
format Online
Article
Text
id pubmed-9450996
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-94509962022-09-08 Polycystin-2 mediates mechanical tension-induced osteogenic differentiation of human adipose-derived stem cells by activating transcriptional co-activator with PDZ-binding motif Wang, Liang Lu, Yahui Cai, Guanhui Chen, Hongyu Li, Gen Liu, Luwei Sun, Lian Guan, Zhaolan Sun, Wen Zhao, Chunyang Wang, Hua Front Physiol Physiology Human adipose-derived stem cells (hASCs) have multi-directional differentiation potential including osteogenic differentiation. Mechanical stimulation is thought to be a key regulator of bone remodeling and has been proved to promote osteogenic differentiation of mesenchymal stem cells. However, the mechanism how mechanical tension-induced osteogenesis of hASCs still remains poor understood. Polycystin-2 (PC2), a member of the transient receptor potential polycystic (TRPP) family, is involved in cilia-mediated mechanical transduction. To understand the role of PC2 in osteogenic differentiation under mechanical stimuli in hASCs, PKD2 gene was stably silenced by using lentivirus-mediated shRNA technology. The results showed that mechanical tension sufficiently enhanced osteogenic differentiation but hardly affected proliferation of hASCs. Silencing PKD2 gene caused hASCs to lose the ability of sensing mechanical stimuli and subsequently promoting osteogenesis. PC2 knock-out also reduced the cilia population frequency and cilia length in hASCs. TAZ (transcriptional coactivator with PDZ-binding motif, also known as Wwtr1) could mediate the genes regulation and biological functions of mechanotransduction signal pathway. Here, mechanical tension also enhanced TAZ nuclear translocation of hASCs. PC2 knock-out blocked tension-induced upregulation of nuclear TAZ and suppress tension-induced osteogenesis. TAZ could directly interact with Runx2, and inhibiting TAZ could suppress tension-induced upregulation of Runx2 expression. In summary, our findings demonstrated that PC2 mediate mechanical tension-induced osteogenic differentiation of hASCs by activating TAZ. Frontiers Media S.A. 2022-08-24 /pmc/articles/PMC9450996/ /pubmed/36091380 http://dx.doi.org/10.3389/fphys.2022.917510 Text en Copyright © 2022 Wang, Lu, Cai, Chen, Li, Liu, Sun, Guan, Sun, Zhao and Wang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Wang, Liang
Lu, Yahui
Cai, Guanhui
Chen, Hongyu
Li, Gen
Liu, Luwei
Sun, Lian
Guan, Zhaolan
Sun, Wen
Zhao, Chunyang
Wang, Hua
Polycystin-2 mediates mechanical tension-induced osteogenic differentiation of human adipose-derived stem cells by activating transcriptional co-activator with PDZ-binding motif
title Polycystin-2 mediates mechanical tension-induced osteogenic differentiation of human adipose-derived stem cells by activating transcriptional co-activator with PDZ-binding motif
title_full Polycystin-2 mediates mechanical tension-induced osteogenic differentiation of human adipose-derived stem cells by activating transcriptional co-activator with PDZ-binding motif
title_fullStr Polycystin-2 mediates mechanical tension-induced osteogenic differentiation of human adipose-derived stem cells by activating transcriptional co-activator with PDZ-binding motif
title_full_unstemmed Polycystin-2 mediates mechanical tension-induced osteogenic differentiation of human adipose-derived stem cells by activating transcriptional co-activator with PDZ-binding motif
title_short Polycystin-2 mediates mechanical tension-induced osteogenic differentiation of human adipose-derived stem cells by activating transcriptional co-activator with PDZ-binding motif
title_sort polycystin-2 mediates mechanical tension-induced osteogenic differentiation of human adipose-derived stem cells by activating transcriptional co-activator with pdz-binding motif
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9450996/
https://www.ncbi.nlm.nih.gov/pubmed/36091380
http://dx.doi.org/10.3389/fphys.2022.917510
work_keys_str_mv AT wangliang polycystin2mediatesmechanicaltensioninducedosteogenicdifferentiationofhumanadiposederivedstemcellsbyactivatingtranscriptionalcoactivatorwithpdzbindingmotif
AT luyahui polycystin2mediatesmechanicaltensioninducedosteogenicdifferentiationofhumanadiposederivedstemcellsbyactivatingtranscriptionalcoactivatorwithpdzbindingmotif
AT caiguanhui polycystin2mediatesmechanicaltensioninducedosteogenicdifferentiationofhumanadiposederivedstemcellsbyactivatingtranscriptionalcoactivatorwithpdzbindingmotif
AT chenhongyu polycystin2mediatesmechanicaltensioninducedosteogenicdifferentiationofhumanadiposederivedstemcellsbyactivatingtranscriptionalcoactivatorwithpdzbindingmotif
AT ligen polycystin2mediatesmechanicaltensioninducedosteogenicdifferentiationofhumanadiposederivedstemcellsbyactivatingtranscriptionalcoactivatorwithpdzbindingmotif
AT liuluwei polycystin2mediatesmechanicaltensioninducedosteogenicdifferentiationofhumanadiposederivedstemcellsbyactivatingtranscriptionalcoactivatorwithpdzbindingmotif
AT sunlian polycystin2mediatesmechanicaltensioninducedosteogenicdifferentiationofhumanadiposederivedstemcellsbyactivatingtranscriptionalcoactivatorwithpdzbindingmotif
AT guanzhaolan polycystin2mediatesmechanicaltensioninducedosteogenicdifferentiationofhumanadiposederivedstemcellsbyactivatingtranscriptionalcoactivatorwithpdzbindingmotif
AT sunwen polycystin2mediatesmechanicaltensioninducedosteogenicdifferentiationofhumanadiposederivedstemcellsbyactivatingtranscriptionalcoactivatorwithpdzbindingmotif
AT zhaochunyang polycystin2mediatesmechanicaltensioninducedosteogenicdifferentiationofhumanadiposederivedstemcellsbyactivatingtranscriptionalcoactivatorwithpdzbindingmotif
AT wanghua polycystin2mediatesmechanicaltensioninducedosteogenicdifferentiationofhumanadiposederivedstemcellsbyactivatingtranscriptionalcoactivatorwithpdzbindingmotif